Role of plasma fatty acid in age-related macular degeneration: insights from a mendelian randomization analysis.

BACKGROUND: An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes. METHODS: We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides. RESULTS: Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD. CONCLUSIONS: The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.

Research Progress in Modifications, Bioactivities, and Applications of Medicine and Food Homologous Plant Starch.

Starchy foods are an essential part of people's daily diet. Starch is the primary substance used by plants to store carbohydrates, and it is the primary source of energy for humans and animals. In China, a variety of plants, including edible medicinal plants, such as Pueraria root, yam tuber and coix seed, are rich in starch. However, limited by their inherent properties, kudzu starch and other starches are not suitable for the modern food industry. Natural starch is frequently altered by physical, chemical, or biological means to give it superior qualities to natural starch as it frequently cannot satisfy the demands of industrial manufacturing. Therefore, the deep processing market of modified starch and its products has a great potential. This paper reviews the modification methods which can provide excellent functional, rheological, and processing characteristics for these starches that can be used to improve the physical and chemical properties, texture properties, and edible qualities. This will provide a comprehensive reference for the modification and application of starch from medicinal and edible plants.

3D printed fibroblast-loaded hydrogel for scleral remodeling to prevent the progression of myopia.

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

Application of IPSC and Müller glia derivatives in retinal degenerative diseases.

Retinal degenerative diseases cause blindness characterized by a progressive decline in the number and function of retinal pigment epithelium (RPE), photoreceptor cells, and ganglion cells. Such diseases include retinitis pigmentosa (RP), glaucomatous optic neuropathy, age-related macular degeneration and diabetic optic neuropathy. Recent studies have demonstrated that Müller glial cells (MGCs), an endogenous alternative source of retinal neurons, are important glial cells involved in retinal development, damage, and regeneration, making it an excellent target for retinal nerve regeneration. Although hardly differentiate into neuron cells, transplanted MGCs have been shown to induce partial recovery of visual function in experimental retinal degenerative models. This improvement is possibly attributed to the release of neuroprotective factors that derived from the MGCs. With the development of the therapeutic usage of pluripotent stem cell, application of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) originated derivation of MGCs have been widely used in retinal degenerative disease model such as glaucoma and retinitis pigmentosa model. This chapter summarized the relevant research and mechanisms and provided a broader application and research prospects for effective treatments in retinal degenerative diseases.

Retinal Neurotransmitter Alteration in Response to Dopamine D2 Receptor Antagonist from Myopic Guinea Pigs.

This study aimed to investigate the changes in retinal neurotransmitters and the role of the dopamine D2 receptor (D2R) pathway in regulating the myopic refractive state. Tricolor guinea pigs were randomly divided into two groups: the normal control group (NC) and the form-deprivation myopia group (FDM). Animals in the FDM group had their right eye covered with a balloon for 4 weeks. These two groups were further divided into two subgroups based on intravitreal injection with D2R antagonist sulpiride once a week for 3 weeks (NC, NC-Sul, FDM, and FDM-Sul groups). Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to quantitatively detect the changes in 17 retinal neurotransmitters. Compared to the NC group, the concentrations of dopamine (DA) and γ-aminobutyric acid (GABA) decreased, while those of glutamate (Glu), 3-methoxytyramine (3-MT), and glycine increased, accompanied by an increase in myopic refraction and axial length (AL) in the FDM group. In the FDM-Sul group, glycine and DA levels were upregulated, whereas 3-MT and Glu levels were downregulated, accompanied by a decrease in myopic refraction and AL. The ratio of Glu to GABA (RGG) represents the balance between excitatory and inhibitory neurotransmitters. Notably, RGG changes occurred with corresponding AL changes, which increased in the FDM group and decreased in the FDM-Sul group. Decreased retinal DA concentration, with an increase in Glu, may be involved in the myopia progression. D2R antagonists might effectively slow myopia progression by increasing retinal DA, regulating Glu concentration to match GABA, and maintaining the balance between excitatory and inhibitory neurotransmitters.

Effects of dopamine D2 receptor antagonists on retinal pigment epithelial/choroid complex metabolism in form-deprived myopic guinea pigs.

The retinal pigment epithelial (RPE)/choroid complex regulates myopia development, but the precise pathogenesis of myopia remains unclear. We aimed to investigate the changes in RPE/choroid complex metabolism in a form deprivation myopia model after dopamine D2 receptor (D2R) modulation. Guinea pigs were randomly divided into normal (NC), form deprivation myopia (FDM), and FDM treated with dopamine D2R antagonist groups. Differential metabolites were screened using SIMCA-P software and MetaboAnalyst metabolomics analysis tool. Functions of differential metabolites were analyzed using KEGG enrichment pathways. Relative to the NC group, 38 differential metabolites were identified, comprising 29 increased metabolites (including nicotinic acid, cytosine, and glutamate) and 9 decreased metabolites, of which proline exhibited the largest decrease. Pathway analysis revealed regulation of arginine/proline and aspartate/glutamate metabolism. Intravitreal D2R antagonist injection increased proline concentrations and activated arginine/proline and purine metabolism pathways. In sum, D2R antagonists alleviated the myopia trend of refractive biological parameters in form deprivation myopic guinea pigs, suggesting the involvement of dopamine D2R signaling in myopia pathogenesis. The RPE/choroid may provide glutamate to the retina by activating proline metabolism via metabolic coupling with the retina. Dopamine D2R antagonism may modulate proline/arginine metabolic pathways in the RPE/choroid and regulate metabolism, information presentation, and myopia.

High-Fat Diet Alters Acylcarnitine Metabolism of the Retina and Retinal Pigment Epithelium/Choroidal Tissues in Laser-Induced Choroidal Neovascularization Rat Models.

SCOPE: Choroidal neovascularization (CNV) is age-related macular degeneration's (AMD) main pathological change. High-fat diet (HFD) is associated with a form of CNV; however, the specific mechanism is unclear. Mitochondrial dysfunction, characterized by abnormal acylcarnitine, occurs during metabolic screening of serum or other body tissues in AMD. This study investigates HFD's role in retinal and retinal pigment epithelium (RPE)/choroidal acylcarnitine metabolism in CNV formation. METHODS AND RESULTS: Chow diet and HFD-BN rats are laser-treated to induce CNV. Acylcarnitine species are quantitatively characterized by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Optical coherence tomography and fundus fluorescein angiography evaluate CNV severity. HFD promotes weight gain, dyslipidemia, and CNV formation. In CNV rats, few medium-chain fatty acids (MCFAs) acylcarnitine in the RPE/choroid are initially affected. When an HFD is administered to these, even MCFA acylcarnitine in the RPE/choroid is found to decline. However, in the retina, odd acylcarnitines are increased, revealing "an opposite" change within the RPE/choroid, accompanied by influencing glycolytic key enzymes. The HFD+CNV group incorporated fewer long-chain acylcarnitines, like C18:2, into the retina than controls. CONCLUSIONS: HFD hastens choroidal neovascularization. The study comprehensively documented acylcarnitine profiles in a CNV rat model. Acylcarnitine's odd-even and carbon-chain length properties may guide future therapeutics.

Short-term clinic observation of misalignment and rotational stability after implantable collamer lens implantation.

PURPOSE: We aimed to investigate misalignment (tilt and decentration) and rotational stability of the implantable collamer lens V4c 6 months after implantation and to explore the potential risk factors associated with postoperative misalignment and rotation. METHODS: A total of 36 eyes of 36 patients with high myopia and myopic astigmatism who underwent implantable collamer lens V4c implantation were included in this study. Tilt, decentration, and rotation of the implantable collamer lens were assessed postoperatively at l week, 1 month, 3 months, and 6 months. Correlation analysis was used to identify the potential risk factors for implantable collamer lens tilt, decentration, and rotation at 6 months postoperatively. Higher-order aberration was measured to evaluate the effect of implantable collamer lens misalignment on visual quality at pupil diameters of 4.0 mm and 6.0 mm. RESULTS: The tilt and decentration at the last follow-up were 2.43 ± 1.35° and 0.278 ± 0.160 mm, respectively. There was a significant positive correlation between tilt and decentration (r = 0.31, P = 0.046). No significant correlation was detected between implantable collamer lens decentration and internal higher-order aberrations (P > 0.05). The degree of implantable collamer lens rotation (3.11 ± 2.00°) was significantly associated with the vault (r = - 0.422, P = 0.01), while it was positively associated with the preoperative anterior chamber depth (r = 0.36, P = 0.034). No significant correlation was found between postoperative astigmatism and rotation (r = - 0.07, P = 0.351). CONCLUSIONS: The implantable collamer lens V4c provides relatively stable misalignment and rotation after implantation. The ICL lens vault is a potential risk factor for postoperative implantable collamer lens rotation. The absolute value of decentration and tilt was relatively small, which showed no correlation with internal higher-order aberration in short-term observation.

Metabolic Characterization of Ocular Tissues in Relation to Laser-Induced Choroidal Neovascularization in Rats.

Age-related macular degeneration is a metabolic compromise disorder whose main pathological feature is choroidal neovascularization (CNV) formation. Using untargeted metabolomics analysis, we determined to assess the metabolomic alterations in a CNV rat model to provide an insight into its pathogenesis. In the CNV model, there were 24 significantly changed metabolites in the plasma and 71 in various ocular tissues. Pathway analysis showed that certain metabolic pathways changed in interrelated tissues: for instance, in terms of the altered urea cycle, arginine and proline metabolism were increased in the plasma, while spermidine and spermine biosynthesis activities were increased in the retinal pigment epithelium (RPE)/choroid. The retina and RPE/choroid shared the same changed metabolites of branched-chain amino acid metabolism. Fatty acid metabolism was found to be the significant altered metabolic pathway in the retina of this CNV model. Although the metabolism pattern of different substances is specific for each ocular tissue, there is also a certain material exchange between different tissues. Dysregulated metabolomic profiles in differential tissues may point to an interconnected pathway, oxidative stress response, which may lead to RPE cell degeneration and, ultimately, CNV development.

[Effect of acupuncture on retinal and choroidal thickness in patients with optic atrophy].

OBJECTIVE: To observe the effect of acupuncture on visual acuity, intraocular pressure, visual field, retinal and choroidal thickness on optic disc and macular area in patients with optic atrophy. METHODS: A total of 33 patients with optic atrophy were treated with acupuncture. Acupuncture was given at Chengqi (ST 1), Shangjingming (Extra), Qiuhou (EX-HN 7) and Fengchi (GB 20) etc., 30 min each time, once a day, for 14 days. The visual acuity, intraocular pressure, visual field indexes (mean deviation [MD], pattern standard deviation [PSD] and visual field index [VFI]), optic disc retinal nerve fiber layer thickness, macular retinal thickness and choroidal thickness of optic disc and sub-foveal were compared before and after treatment. RESULTS: Compared before treatment, the visual acuity was increased (P<0.05), the MD value was decreased (P<0.05), the thickness of nerve fiber layer on the upper temporal side of optic disc was thinner (P<0.05), and the choroidal thickness of average, nasal side and lower temporal side of optic disc was increased (P<0.05). There was significant correlation between visual field MD and retinal nerve fiber layer thickness in different quadrants before and after treatment (P<0.01). CONCLUSION: Acupuncture could improve visual acuity, increase choroidal thickness in part of optic disc area in patients with optic atrophy.

Comparison of the visual performance of iris-fixated phakic lens and implantable collamer lens to correct high myopia.

BACKGROUND: To compare visual performance between the iris-fixated phakic intraocular len (pIOL) and implantable collamer len (ICL) to correct high myopia. METHODS: Twenty-four eyes underwent iris-fixated pIOL implantation and 24 eyes underwent ICL implantation. At the 6-month follow-up, the best-corrected visual acuity (BCVA) and uncorrected distance visual acuity (UDVA) were compared between the iris-fixated pIOL and ICL groups. The objective scatter index (OSI), modulation transfer function (MTF) cutoff, and ocular aberrations were performed to evaluate postoperative visual quality between the two groups. RESULTS: No significant difference was found in UDVA, BCVA, and spherical equivalent between the iris-fixated pIOL and ICL groups (P > 0.05). Six months after surgery, the following values were significantly higher in the ICL group than in the iris-fixated pIOL group: MTF cutoff, strehl ratio and optical quality analysis system values at contrasts of 9 %, 20 %, and 100 % (P < 0.01). The OSI in the iris-fixated pIOL group was higher than in the ICL group 6 months after surgery (P < 0.01). All high-order aberrations were slightly more severe in the iris-fixated pIOL group than in the ICL group 6 months after surgery, although only trefoil (P = 0.023) differed significantly in this regard. CONCLUSIONS: Both iris-fixated lenses and ICLs can provide good visual acuity. ICLs confer better visual performance in MTF-associated parameters and induce less intraocular light scattering than iris-fixated pIOLs.

Distribution and analysis of intraocular pressure and its possible association with glaucoma in children.

PURPOSE: To analyze intraocular pressure (IOP) and glaucoma-associated factors in children. METHODS: A total of 4438 children aged 7-16 years (2321 boys and 2117 girls) were included in this study. Various ophthalmologic [IOP, central corneal thickness (CCT), etc.] and demographic (body mass index, etc.) parameters were evaluated. RESULTS: IOP increased between the ages of 7 and 9 years, peaking at 9 years. IOP increased after reaching a trough at 11 years and subsequently stabilized after 14 years. Girls exhibited thinner CCT (534.28 ± 30.84 µm vs. 537.04 ± 31.33 µm, P = 0.003), thicker lens thickness (3.56 ± 0.21 mm vs. 3.54 ± 0.20 mm, P = 0.001), shorter axial length (22.91 ± 0.93 mm vs. 23.32 ± 0.89 mm, P < 0.001), shallower anterior chamber depth (2.92 ± 0.27 mm vs. 3.00 ± 0.26 mm, P < 0.001), higher refraction (- 0.57 ± 1.48 D vs. 0.16 ± 1.35 D, P < 0.001), and higher mean corneal curvature (43.77 ± 1.39 vs. 43.03 ± 1.35, P < 0.001). Multivariable analysis assessed the following IOP-associated factors: thicker CCT [standardized correlation coefficient (SRC) = 0.201, P < 0.001), deeper anterior chamber depth (SRC = 0.059, P = 0.009), shorter axial length (SRC = - 0.086, P = 0.036), lower mean corneal curvature (SRC = - 0.123, P < 0.001), higher refraction (SRC = - 0.090, P < 0.001). CONCLUSION: IOP fluctuated in children, and a trend toward a higher mean IOP between the ages of 9 and 11 years, which stabilized after 14 years, was observed. IOP was associated with CCT, anterior chamber depth, axial length, lens thickness, mean corneal curvature, spherical equivalent, and systolic blood pressure.

Effect of biomechanical properties on myopia: a study of new corneal biomechanical parameters.

BACKGROUND: To assess the corneal stress-strain index (SSI), which is a marker for material stiffness and corneal biomechanical parameters, in myopic eyes. METHODS: A total of 1054 myopic patients were included in this study. Corneal visualisation Scheimpflug technology was used to measure the SSI. Corneal biomechanics were assessed using the first and second applanation times (A1-and A2-times); maximum deflection amplitude (DefAmax); deflection area (HCDefArea); the highest concavity peak distance (HC-PD), time (HC-time), and deflection amplitude (HC-DefA); integrated radius (IR); whole eye movement (WEM); stiffness parameter (SP-A1;, biomechanically corrected intraocular pressure (BIOP); and Corvis biomechanical index (CBI). Scheimpflug tomography was used to obtain the mean keratometery (Km) and central corneal thickness (CCT). According to the spherical equivalent (SE) (low myopia: SE ≥ - 3.00D and high myopia: SE ≤ - 6.00D.), the suitable patients were divided into two groups. RESULTS: The mean SSI value was 0.854 ± 0.004. The SSI had a positive correlation with A1-time ((r = 0.272), HC-time (r = 0.218), WEM (r = 0.288), SP-A1 (r = 0.316), CBI (r = 0.199), CCT (r = 0.125), bIOP (r = 0.230), and SE (r = 0.313) (all p-values<0.01). The SSI had a negative correlation with HCDefA (r = - 0.721), HCDefArea (r = - 0.665), HC-PD(r = - 0.597), IR (r = - 0.555), DefAmax (r = - 0.564), and Km (r = - 0.103) (all p-values<0.01). There were significant differences in SSI (t = 8.960, p<0.01) and IR (t = - 3.509, p<0.01) between the low and high myopia groups. CONCLUSIONS: In different grades of myopia, the SSI values were lower in eyes with higher SEs. It indicates that the mechanical strength of the cornea may be compromised in high myopia. The SSI was positively correlated with the spherical equivalent, and it may provide a new way to study the mechanism of myopia.

Metabolomic analysis of the aqueous humor from patients with central retinal vein occlusion using UHPLC-MS/MS.

Central retinal vein occlusion (CRVO) is one of the retinal fundus diseases and may result in irreversible visual impairment. Metabolic dysfunction has been proved to play an essential role in the pathogenesis of CRVO. We performed untargeted metabolomic analysis of the aqueous humor (AH) of patients with CRVO and controls using UHPLC-MS/MS. A total of 248 metabolites were identified in the tested AH samples, 37 of which allowed for the construction of an orthogonal partial least squares discriminant analysis model with good predictive capability (Q2cum = 0.834) and low risk of overfitting. The components contributing the most to the metabolomic signature of CRVO were those related to amino acid metabolism, carbohydrates, and fatty acid metabolites (variable importance on projection>1.0 and p < 0.05). The CRVO group appeared to have a lower AH concentration of carbohydrates and amino acids, but a relative higher concentration of carnitine-associated energetic substrates (butyryl carnitine, deoxycarnitine, N6-trimethyl-l-lysine) and osmolytes compared with those of the control group. These results indicate that patients with CRVO may have ocular aberrations in metabolic pathways involving certain amino acids, fatty acids, and carbohydrates. These metabolite changes might correlate with energy dysfunction and inflammation response in the AH of CRVO patients. This finding may provide insight into the pathophysiology of CRVO for the development of new therapeutic strategies.

Changes in Corneal Volume at Different Areas and Its Correlation with Corneal Biomechanics after SMILE and FS-LASIK Surgery.

PURPOSE: To investigate the variations of corneal volume (CV) after small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and analyze the influences of biomechanical properties on the changes of refraction and CV. METHODS: Ninety-seven eyes of 97 patients undergoing SMILE and FS-LASIK were included in this retrospective study. CV was measured with Scheimpflug-based corneal topography at preoperatively and at day 1, week 1, and months 1 and 3 postoperatively. CV measured within 5 mm diameter was defined as central region volume (CV5) and between 5 mm and 10 mm diameter was defined as peripheral region volume (CV5-10). An Ocular Response Analyzer (ORA) was used to assess corneal biomechanical properties including corneal hysteresis (CH) and corneal resistant factor (CRF). The reduction of study parameters (△) were calculated by subtracting the preoperative value at various time points from the postoperative values. RESULTS: CV had significant reduction after the SMILE and FS-LASIK procedure (P < 0.05). CV5 increased significantly from postoperative day 1 to month 3 (P < 0.001) in SMILE, while both CV5 and CV5-10 increased significantly in FS-LASIK (P < 0.001). The increase in CV5 after SMILE was 0.11 ± 0.16 mm3，which was significantly different from FS-LASIK (0.20 ± 0.13 mm3, P=0.004). In the SMILE group, △CV5 correlated with △CRF (r = 0.498, P < 0.001) and △CH (r = 0.374, P=0.007). In the FS-LASIK group, △CV5 and △CRF had a significant correlation (r = 0.363, P=0.012), but not with △CH. CONCLUSIONS: Dynamic changes in corneal volume were found after SMILE and FS-LASIK surgery. The central region significantly increased after SMILE, while both central and peripheral regions increased following FS-LASIK in the early postoperative period. SMILE was associated with less change in biomechanical properties per unit of reduction in CV compared with FS-LASIK.

The Differential Expression of Cytokines and Growth Factors After SMILE Compared With FS-LASIK in Rabbits.

Purpose: To investigate the differential expression of cytokines and growth factors in the cornea and aqueous humor after small incision lenticule extraction (SMILE) compared with femtosecond LASIK (FS-LASIK) using rabbit model. Methods: Sixteen eyes of 16 rabbits in each group underwent SMILE or FS-LASIK with refractive correction of -6.00 DS/-1.00 DC. Eight additional rabbits served as controls. Pre- and 24 hours, 1 week, 1 month, and 3 months postoperatively, slit-lamp and anterior segment optical coherence tomography were performed, followed by cornea and aqueous humor collection. Apoptosis and proliferation were evaluated with TUNEL assay and Ki-67 immunostaining, respectively. The mRNA and protein expression of cytokines and growth factors was determined by RT-qPCR and Western blotting, respectively. Cytokine levels in the aqueous humor were detected with ELISA. Results: Compared with FS-LASIK, SMILE induced less apoptosis and proliferation in the cornea within 1 week postoperatively. Levels of IL-1ß, TNF-α, and EGFR in the cornea were significantly increased after FS-LASIK compared with SMILE within 24 hours. Levels of IL-8 in the aqueous humor remained elevated until 1 week after FS-LASIK but not SMILE. TGF-ß1 level was elevated up to 1 month after both procedures, while BFGF level was kept high within 1 month after SMILE but not FS-LASIK. Conclusions: SMILE could induce significantly less acute inflammation than FS-LASIK in the cornea and aqueous humor. The differential expression of TGF-ß1 and BFGF between two procedures until 1 month might contribute to the post-SMILE delayed recovery and underline the importance of continued treatment postoperatively.

Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration.

Purpose: Energy compromise underpins wet age-related macular degeneration (wAMD) pathogenesis, but the relationship between glucose metabolism and the disease remains unclear. Here, we characterized aqueous humor (AH) to elucidate glucose-related metabolic signatures in patients with wAMD. Methods: In total, 25 eyes of 25 patients with wAMD were divided into phakic (15 eyes), pseudophakic (10 eyes), and intravitreal injections of ranibizumab (13 eyes) wAMD groups. Twenty patients with cataract (21 eyes) served as controls. Ultrahigh-performance liquid chromatography tandem mass spectrometry was used to quantitatively characterize AH. Results: Twenty-one metabolites related to glucose metabolism were identified in AH from 45 patients. Tricarboxylic acid (TCA)-related metabolic substrates, including citrate, were detected in AH and were significantly increased in AMD (P < 0.01) and AMD pseudophakic groups (P < 0.05). In contrast, α-ketoglutarate levels were decreased in the AMD group (P < 0.05). The α-ketoglutarate/citrate ratio was significantly decreased, corresponding to 71.71% and 93.6% decreases in the AMD (phakic and pseudophakic) groups as compared with controls (P < 0.001), revealing a significant positive correlation with glutamine. A lower mean glutamine and higher glutamate level were detected in AMD cases compared with controls. No significant differences were observed for lactic acid or other Krebs cycle metabolites. Intravitreal injection significantly alleviated mean central foveal thickness but did not significantly alter metabolites. Conclusions: Compromised glucose TCA cycle and altered glutamine metabolism are implicated in the AH metabolism in wAMD. These findings highlight potential treatments for alleviating wAMD from a metabolic perspective.

Metabolomic Profiling of the Aqueous Humor in Patients with Wet Age-Related Macular Degeneration Using UHPLC-MS/MS.

Assessing metabolomic alterations in age-related macular degeneration (AMD) can provide insights into its pathogenesis. We compared the metabolomic profiles of the aqueous humor between wet AMD patients (n = 26) and age- and sex-matched patients undergoing cataract surgery without AMD as controls (n = 20). A global untargeted metabolomics study was performed using ultra-high-performance liquid chromatography tandem mass spectrometry. Univariate analysis after the false discovery correction showed 18 significantly altered metabolites among the 291 metabolites measured. These differential metabolomic profiles pointed to three interconnected metabolic pathways: a compromised carnitine-associated mitochondrial oxidation pathway (carnitine, deoxycarnitine, N6-trimethyl-l-lysine), an altered carbohydrate metabolism pathway (cis-aconitic acid, itaconatic acid, and mesaconic acid), which plays a role in senescence and immunity, and an activated osmoprotection pathway (glycine betaine, creatine), which potentially contributes to the pathogenesis of the disease. These results suggested that metabolic dysfunction in AMD is mitochondrial-centered and may provide new insights into the pathophysiology of wet AMD and novel therapeutic strategies.

Quantitative analysis of metabolites in glucose metabolism in the aqueous humor of patients with central retinal vein occlusion.

Quantitative analysis of aqueous humor (AH) was performed to investigate glucose metabolism in patients with central retinal vein occlusion (CRVO), and to explore metabolic changes after anti-vascular endothelial growth factor (VEGF) treatment. AH samples were collected from 35 patients. Participants diagnosed with CRVO (n = 15) were compared to participants who underwent cataract surgery (n = 20). Thirteen of the participants with CRVO received second-round anti-VEGF treatments. Ultra-high performance liquid chromatography tandem-mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites of the AH. Central macular thickness (CMT) and retinal ganglion cell layer (RGC) thickness were measured using spectral-domain optical coherence tomography. Thirteen metabolites involved in glucose metabolism were identified. Among these metabolites, succinate, glutamate, and glutamine were significantly decreased for the CRVO group (p = 0.028, 0.009, and 0.017, respectively). The α-ketoglutarate/citrate (K/C) ratio had a significant positive correlation with glutamine levels for both control (r = 0.922, p < 0.001) and CRVO groups (r = 0.674, p = 0.006). A significant increase in lactate was observed after intravitreal anti-VEGF administration (t = 2.273, p = 0.045); the change in CMT was negatively correlated with this increase (r = -0.745, p = 0.003). The alteration of RGC thickness was negatively correlated with increases in both glutamine (r = -0.619, p = 0.024) and glucose (r = -0.754, p = 0.003). These results indicate that, compared to glucose metabolism, glutamine was significantly decreased in the AH of patients with CRVO, and may therefore serve as a potential target for CRVO therapy. The glycolytic pathway might be enhanced after intravitreal anti-VEGF injection, which is an important insight into CRVO pathophysiology.

Real-Time Intraocular Pressure Measurements in the Vitreous Chamber of Rabbit Eyes During Small Incision Lenticule Extraction (SMILE).

PURPOSE: To investigate real-time intraocular pressure (IOP) during small incision lenticule extraction (SMILE) in rabbit eyes for myopia correction. METHODS: During SMILE, real-time IOP was measured in the vitreous cavity of rabbit eyes with an optic fiber pressure sensor (OFPS). Two groups (n = 6 for each) underwent surgery, one group for a -2.00 diopter (D) refractive spherical correction and the other for a -6.00 D correction. RESULTS: During surgery, the IOP increased once the glass contact attached to the cornea (Pre-suction), and peaked 83.94 mmHg (SD ± 23.87 mmHg) for the -2.00 D group and 89.17 mmHg (SD ± 22.66 mmHg) for the -6.00 D group, both average values were less than 110 mmHg when suction was initiated to fix the glass contact onto the cornea (Suction on). It then fell to 74.81 mmHg (SD ± 20.64 mmHg) and 76.94 mmHg (SD ± 27.43 mmHg), respectively, and remained stable during lenticule creation (Cutting). After suction stopped (Suction off), IOP fell steeply. During lenticule separation/extraction, the change in IOP was 32.26 mmHg (SD ± 2.91 mmHg). Notably, the average duration of elevated IOP during the surgery was 166.05 s (no longer than 3 min). CONCLUSIONS: The IOP fluctuations in the vitreous cavity using an OFPS in a rabbit model during SMILE showed that real-time IOP significantly was increased during Pre-suction, Suction on, Cutting, Suction off, and lenticule separation/extraction compared to baseline IOP, although, peaked at Suction on. Neither the degree of myopic correction nor central corneal thickness significantly affected these changes in IOP.