Retinal Damage After Repeated Low-level Red-Light Laser Exposure.

This case report discusses retinal damage incurred after repeated low-level red-light laser exposure in a 12-year-old female patient with a history of myopia.

Three Monthly Injections Versus One Initial Injection of Ranibizumab for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion: 12-Month Results of a Prospective Randomized Study.

INTRODUCTION: To compare three monthly injections versus one initial injection of intravitreal ranibizumab (IVR) followed by pro re nata (PRN) dosing to treat macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: Seventy-four patients were randomized (1:1) to the 3 + PRN or 1 + PRN groups. Patients underwent monthly evaluations and additional IVR injections were administered if the retreatment criteria were met. The functional and anatomical outcomes were recorded. The factors associated with the improvement in best-corrected visual acuity (BCVA) were analyzed. RESULTS: Sixty-nine patients (93.2%) completed the study. At 12 months, the mean gain in BCVA was 12.9 letters in the 3 + PRN group and 14.3 letters in the 1 + PRN group, which was not significant (P = 0.59). The mean reduction in central macular thickness was 297.8 µm in the 3 + PRN group and 300.2 µm in the 1 + PRN group (P = 0.96). The macular vascular density changes of the superficial and deep capillary plexuses were not significantly different between the two groups (P = 0.99 and 0.70, respectively). The mean number of IVR injections was 5.0 in the 3 + PRN group and 4.2 in the 1 + PRN group (P = 0.17). The incidence of retinal neovascularization was similar in both groups (P = 0.67). The baseline BCVA, but not the treatment regimen, was significantly associated with the change in BCVA (P < 0.01). CONCLUSION: Significant gains in BCVA and maintenance of macular perfusion were achieved in BRVO eyes treated with the 3 + PRN or 1 + PRN regimens. Baseline BCVA was a prognostic factor for the visual improvement. TRIAL REGISTRATION: A prospective randomized controlled trial to compare the 1 + PRN and 3 + PRN regimen in the treatment of macular edema secondary to branch retinal vein occlusion (ChiCTR2000038086).

Wide-field swept-source OCT angiography of the periarterial capillary-free zone before and after anti-VEGF therapy for branch retinal vein occlusion.

BACKGROUND: The aim of the study was to investigate the changes in the periarterial capillary-free zone (paCFZ) after anti-vascular endothelial growth factor (VEGF) therapy in patients with branch retinal vein occlusion (BRVO) by wide-field swept-source optical coherence tomography angiography (SS-OCTA) and assess their associations with clinical outcomes. METHODS: In this retrospective observational study of 54 treatment-naïve BRVO patients with macular edema, we reviewed the findings of 12 × 12 mm2 SS-OCTA at baseline, 3, 6, and 12 months after intravitreal ranibizumab injections. The paCFZ and major retinal artery areas were measured on SS-OCTA images. The paCFZ area to artery area (P/A) ratio was calculated. RESULTS: The paCFZ areas and P/A ratios of first- and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes (all P < 0.01), but there were no differences in the first- and second-order artery areas (P = 0.20 and 0.25, respectively). The paCFZ areas and P/A ratios decreased significantly at 3, 6, and 12 months after anti-VEGF therapy (all P < 0.01). The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity (BCVA), central retinal thickness, and their improvements at 3, 6, and 12 months (all P < 0.05). Baseline BCVA and P/A ratios of first- and second-order arteries were independently associated with the final BCVA in multivariate linear regression. CONCLUSIONS: Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in BRVO. Smaller baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.

Photocoagulation-associated spontaneous release of epiretinal membrane secondary to retinal vascular tumor: case series of 8 cases.

To evaluate the secondary epiretinal membrane (ERM) response after photocoagulation in retinal vascular tumor. This retrospective interventional case series included 8 patients (8 eyes) who were diagnosed with retinal vascular tumor and secondary ERM. All eyes were treated with photocoagulation and underwent comprehensive ophthalmologic examinations at baseline and at each follow-up. Of the 8 eyes with retinal vascular tumor and associated ERM, 4 eyes (50%) were von Hippel and 4 eyes (50%) were vasoproliferative tumor of the retina. The mean follow-up time was 12.63 ± 14.64 (range, 4-51) months. The BCVA in the eyes at baseline was 1.16 ± 1.10 logMAR (range, HM to 20/40). ERM located in the macular region in 100% of the eyes and led to CME with a mean central foveal thickness of 497.6 ± 147.7 µm (range, 294-736 µm) at presentation. After photocoagulation, the ERM spontaneously peeled in 7 of 8 eyes (87.5%), among which one case required surgical treatment due to complicating tractional retinal detachment. After ERM peeling without complications, 6 eyes recovered normal macular structure, with an improved BCVA in 5 eyes and a stable BCVA in 1 eye. Laser photocoagulation is necessary and effective treatment for retinal vascular tumor. After laser photocoagulation, retinal vascular tumor-related ERM spontaneously released in 75% of the cases, without complication and surgical intervention.

One-Year Efficacy and Safety of Proton-Beam Irradiation Combined with Intravitreal Conbercept for Refractory or Recurrent Polypoidal Choroidal Vasculopathy: A Pilot Study.

INTRODUCTION: To investigate the efficacy and safety of proton-beam irradiation (PBI) combined with intravitreal conbercept (IVC) injection for refractory or recurrent polypoidal choroidal vasculopathy (PCV). METHODS: A prospective interventional clinical trial included 12 patients with refractory PCV (defined as persistent exudation or fluid after six consecutive injections at monthly intervals and/or photodynamic therapy) or recurrent PCV (defined as new exudative signs after six monthly injections and/or photodynamic therapy) treated between January 2019 and September 2020. Every patient underwent single PBI (14 GyE) with concomitant IVC (0.5 mg) within 1 week and further doses of IVC were administered pro re nata. RESULTS: By the 12-month follow-up, the subretinal fluid was completely absorbed in 9 eyes (81.8%). The angiographic regression and closure rates of the polyps were 60% (12/20) and 90% (18/20), respectively. The mean number of IVC injections was 3.1 ± 1.37. The mean BCVA improved by 20 letters (P = 0.006). The mean central macular thickness (CMT) decreased from 476.50 ± 123.63 µm to 317.70 ± 89.34 µm (P = 0.004). The areas of branching vascular networks and polyps decreased by 37.2% and 72.3%, respectively. Radiation retinopathy was observed in five eyes, but no systemic adverse events were observed. CONCLUSION: PBI combined with IVC appears to promote polyp regression and closure, reduce CMT, and improve BCVA, with a favorable safety profile, after 12 months. Therefore, PBI may be a useful adjuvant therapy for patients with refractory or recurrent PCV. TRIAL REGISTRATION: Proton-Beam Irradiation Combined with Intravitreal Conbercept for Refractory or Recurrent Polypoidal Choroidal Vasculopathy: Prospective Phase II Clinical Study (ChiCTR2000038987).

Role of surfactant protein C in neonatal genetic disorders of the surfactant system: A case report.

RATIONALE: Respiratory distress syndrome (RDS) refers to the symptoms of progressive dyspnea and respiratory failure in newborns shortly after birth. The clinical and genetic characteristics of patients with neonatal RDS have not been extensively reported. PATIENT CONCERNS: A infant was in critical condition with repeated paroxysmal blood oxygen decline. Oxygen inhalation and noninvasive ventilator-assisted breathing relief were not effective. The etiology was unclear, and there was no family history of lung disease. Surface-active substance replacement therapy and positive pressure-assisted ventilation support were ineffective. DIAGNOSIS: The infant was clinically diagnosed with RDS. Genetic tests revealed a heterozygous missense mutation in the c.168 surfactant protein C (SFTPC) gene. INTERVENTIONS: Tracheal intubation was performed with invasive ventilator-assisted breathing, pulmonary surfactant was administered. Supportive treatment for liver protection and administration of a cardiotonic diuretic, vasodilator, human immunoglobulin (intravenous infusion), fresh frozen plasma, and suspended red blood cells were performed. OUTCOMES: The infant showed poor responses to respiratory and circulatory support, antibiotic treatment, and other treatment methods. The patient was discharged from hospital against the advice of us, cut off from us. The long-term prognosis of the patient after discharge remains unknown. LESSONS: SFTPC gene mutations may be an important risk factor for the development of common lung diseases. Because of the important roles of surfactant functions and metabolism, mutations in these genes can affect the production and function of pulmonary surfactant, leading to severe lung disease in term newborns.

Versatile acoustic manipulation of micro-objects using mode-switchable oscillating bubbles: transportation, trapping, rotation, and revolution.

Controllable on-chip multimodal manipulation of micro-objects in microfluidic devices is urgently required for enhancing the efficiency of potential biomedical applications. However, fixed design and driving models make it difficult to achieve switchable multifunction efficiently in a single device. In this study, a versatile bubble-based acoustofluidic device is proposed for multimodal manipulation of micro-objects in a biocompatible manner. Identical bubbles trapped over the bottom microcavities are made to flexibly switch between four different oscillatory motions by varying the applied frequency to generate corresponding modes of streaming patterns in the microchannel. Such regular modes enable stable transportation, trapping, 3D rotation, and circular revolution of the micro-objects, which were experimentally and numerically verified. The mode-switchable manipulations can be noninvasively applied to particles, cells, and organisms with different sizes, shapes, and quantities and can be controlled by key driving parameters. Moreover, 3D cell reconstruction is developed by applying the out-of-plane rotational mode and analyzed for illustration of cell surface morphology while quantifying reliably basic cell properties. Finally, a simple platform is established to integrate user-friendly function control and reconstruction analysis. The mode-switchable acoustofluidic device features a versatile, controllable, and contactless micro-object manipulation method, which provides an efficient solution for biomedical applications.

Long-term outcome of a Chinese cohort idiopathic retinitis, vasculitis, aneurysms, and neuroretinits (IRVAN) patients.

PURPOSE: To evaluate the clinical characteristics and treatment outcomes of idiopathic retinitis, vasculitis, aneurysms, and neuroretinitis (IRVAN) in a cohort of Chinese patients. MATERIALS: The clinical history, imaging evaluation, treatment and outcomes of 42 eyes in 21 patients diagnosed with IRVAN in a 15-year period were reviewed. RESULTS: Most patients were females (90%) ranged from 15 to 58 years old. The initial decimal best corrected visual acuity (BCVA) of the patients ranged from light perception (LP) to 1.5 (0.55 ± 0.38). Eighteen eyes were in stage 2; 21 eyes in stage 3; and 1 in stage 5 at the initial visits according to the present staging system. Two eyes had vitreoretinal fibrovascular proliferation (FVP) and tractional retinal detachment (RD) at the initial visit. Intra-retinal microvascular abnormality (IRMA) was found in 7 eyes. Thirty-four eyes received retinal photocoagulation, 27 of which were pan-retinal photocoagulation (PRP). Total of 8 PPV were performed for VH, vitreoretinal FVP and RD, and macular epimembrane. Aneurysms on the head of optic nerve and artery bifurcations disappeared in 8 eyes and decreased in number in 2 eyes 1 year after photocoagulation. However, the BCVA of the patients did not have significant difference from that at the initial visits (P = 0.534). Seven eyes suffered severe visual impairment (BCVA ≤ 0.1) due to vitreoretinal FVP and tractional RD (3), exudative maculopathy (2), paracentral acute middle maculopathy (PAMM)(1), and neovascular glaucoma (NVG) (1). CONCLUSIONS: We found that IRVAN have a predilection to female gender. Vitreoretinal FVP and tractional RD and exudative maculopathy are major causes of severe visual impairment in IRVAN patients. We propose to revise the present staging system to include vitreoretinal FVP and RD in the staging of IRVAN patients.

Wide-Field Swept-Source Optical Coherence Tomography Angiography Analysis of the Periarterial Capillary-Free Zone in Branch Retinal Vein Occlusion.

Purpose: To investigate the characteristics of the retinal periarterial capillary-free zone (paCFZ) with wide-field swept-source optical coherence tomography angiography (SS-OCTA) in eyes with branch retinal vein occlusion (BRVO). Methods: Seventy treatment-naïve eyes with BRVO and 35 healthy eyes were included. The paCFZ areas, artery calibers, and areas of the major arteries in the unaffected quadrants of BRVO eyes were measured in 12 × 12-mm SS-OCTA images and compared with those of the contralateral eyes and healthy eyes. Other multimodal imaging data were collected. Results: There were no significant differences in the unaffected artery caliber or area among the three groups (all P > 0.05). The unaffected paCFZ areas and the ratios of the unaffected paCFZ area to the counterpart artery area (paCFZ/artery area) of the major arteries were significantly larger than those in the contralateral or healthy eyes (all P < 0.05). Subgroup analysis revealed that the paCFZ/artery area value differed significantly between ischemic and nonischemic BRVO eyes (P < 0.01). The paCFZ/artery area value was positively correlated with logMAR best-corrected visual acuity, symptom duration, central macular thickness, and retinal nonperfusion area in BRVO. Conclusions: Quantitative SS-OCTA measurements confirmed enlarged paCFZs along the unaffected major retinal arteries in BRVO eyes. The paCFZ parameters were correlated with symptom duration, retinal ischemia, and visual function. Translational Relevance: Retinal periarterial capillary-free zones in BRVO can be non-invasively measured by SS-OCTA, assisting in clinically identifying retinal ischemia and evaluating visual function.

Quantitative evaluation of hard exudates in diabetic macular edema by multicolor imaging and their associations with serum lipid levels.

AIMS: To quantify hard exudates (HEs) by multicolor imaging (MCI) and traditional color fundus photography (CFP) in diabetic macular edema (DME), and study their associations with serum lipid levels. METHODS: Observational study. DME patients with HEs were recruited. The HE area and location both by MCI and CFP were measured by ImageJ software. Multivariate regression models were used to analyze the associations of serum lipid levels with the total HE area and HE location. RESULTS: Sixty-two patients (74 eyes) were enrolled to quantify HEs in DME. The total HE area by MCI was larger than that by CFP (P = 0.004), and the distance between the fovea and the nearest HE by MCI was shorter than that by CFP (P = 0.003). The percentage of patients with HEs involving the central macula by MCI was significantly higher than that by CFP (P < 0.001). Furthermore, 62 eyes of 62 patients were included to analyze the associations of HE parameters with serum lipid levels. In both MCI and CFP, the HE areas were positively associated with triglyceride level (P = 0.016, P = 0.022, respectively). HEs involving the central macula were positively associated with triglyceride and low-density cholesterol levels in MCI (P = 0.028, P = 0.046, respectively), while no significant association was found between serum lipid levels and HE location in CFP. CONCLUSIONS: MCI is superior to traditional CFP for the detection of HEs and the analysis of associations between HEs and serum lipid levels in DME.

Ferrostatin-1 attenuates ferroptosis and protects the retina against light-induced retinal degeneration.

Degenerative retinal diseases, including age-related macular degeneration, are serious diseases that may lead to irreversible retinal neuron damage and permanent vision impairment. There are currently no effective treatments for these diseases due to our incomplete understanding of the underlying pathological mechanisms. Ferroptosis, a newly identified iron-dependent mode of cell death, is implicated in various diseases. However, it is unknown whether ferroptosis is involved in light-induced retinal degeneration. In this study, we found that light exposure significantly reduced the viability of photoreceptor cells in vitro and induced pro-ferroptotic changes, including iron accumulation, mitochondrial shrinkage, glutathione depletion, increased malondialdehyde (MDA), and decreased protein expression of SLC7A11 and GPX4. The effects of light exposure on ferroptosis were attenuated by ferrostatin-1. Consistently, the results of in vivo studies demonstrated that ferrostatin-1 protected against light-induced ferroptosis. And it exerted therapeutic effects by inhibiting neuroinflammation and prevented the effects of light exposure on the structure and function of the retina. The findings reveal an important role of ferroptosis in the pathogenesis of light-induced retinal degeneration and suggest that ferroptosis may be a novel treatment target for preventing retinal degeneration.

CLINICAL FEATURES OF FLAT IRREGULAR PIGMENT EPITHELIAL DETACHMENT ASSOCIATED WITH CHOROIDAL NEOVASCULARIZATION IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To describe the multimodal imaging characteristics of flat irregular pigment epithelial detachment (FIPED) in patients with chronic central serous chorioretinopathy and determine the risk factors for vascularized FIPED and to explore the activity of vascularized FIPED before and after half-dose photodynamic therapy. METHODS: Multimodal imaging data of 185 eyes of 155 consecutive patients with chronic central serous chorioretinopathy included spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Optical coherence tomography angiography was available for 56 eyes. Flat irregular PED was classified into two types based on indocyanine green angiography or optical coherence tomography angiography findings: avascular FIPED and vascularized FIPED. RESULTS: The avascular FIPED and vascularized FIPED were detected in 127 (68.6%) and 42 (22.7%) eyes, respectively. Age (P = 0.001), visual acuity (P = 0.048), subfoveal choroidal thickness (P = 0.032), height (P < 0.001) and width (P < 0.001) of FIPED, choriocapillary thickness (P = 0.015), and maximum vessel diameter (P = 0.009) beneath the FIPED were significantly different between avascular and vascularized FIPEDs. Old age was an independent risk factor for vascularized FIPED. On optical coherence tomography angiography, all vascularized FIPEDs manifested the pattern of mature choroidal neovascularization (CNV). After half-dose photodynamic therapy, vascularized FIPED remained stable without the reaccumulation of subretinal fluid at the last follow-up. CONCLUSION: In chronic central serous chorioretinopathy, vascularized FIPED was closely associated with Type I CNV. Old age was an independent risk factor for vascularized FIPED. Vascularized FIPED is suggested as "quiescent" CNV, and half-dose photodynamic therapy may be recommended as the first-line therapy in chronic central serous chorioretinopathy complicated with quiescent CNV, except when the activity of CNV becomes evident.

OCTA evaluation of treatment-naïve flat irregular PED (FIPED)-associated CNV in chronic central serous chorioretinopathy before and after half-dose PDT.

BACKGROUND: To qualitatively and quantitatively evaluate the features of treatment-naïve flat irregular pigment epithelial detachment (FIPED)-associated choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSC) using swept-source (SS) optical coherence tomography angiography (OCTA) before and after half-dose photodynamic therapy (PDT). METHODS: Retrospective case series. The multimodal imaging data of the eyes with FIPED-associated CNV in chronic CSC were reviewed. The features of FIPED-associated CNVs were evaluated by SS-OCTA. RESULTS: Records of twenty-one patients (21 eyes) were reviewed. The mean age was 56.62 ± 6.87 years. After half-dose PDT, all patients have improved best spectacle-corrected visual acuity from 0.49 at baseline to 0.25 at 6-month visit, and subfoveal choroidal thickness decreased with subretinal fluids absorbed. By OCTA, the features of CNV at baseline included long filamentous linear vessels (21/21), branching into other large mature vessels with rare anastomoses (21/21); and/or a 'dead tree' appearance at the vessel's termini (20/21); and no perilesional hypointense halo (21/21). Compared to those at baseline, the mean vessel density of CNV showed no significant change at 1-,3-,6-month follow-up, while the mean area of CNV was significantly larger at the 6-month follow-up (p = 0.013). CONCLUSIONS: OCT angiography allows to qualitatively and quantitatively evaluate CNV in chronic CSC. The features of FIPED-associated CNV on OCTA illustrated its quiescent characteristic and further guided therapy. Half-dose PDT showed favorable effects on chronic CSC complicated with FIPED-associated CNV.

A case report of ultrasonographic findings in bilateral diffuse Uveal melanocytic proliferation.

BACKGROUND: To report undescribed characteristics of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) on ultrasound biomicroscopy (UBM) and high-frequency B-scan ultrasonography. CASE PRESENTATION: Two of four participants presented with worsening bilateral vision after previously diagnosed primary pulmonary or ovarian carcinoma. The other two patients were diagnosed with lung carcinoma after presentation with BDUMP. All patients had ciliary body nevi-like lesion in combination with iris or ciliary body cysts, and uveal thickening on UBM. Focally elevated choroidal nevi-like lesion and exudative retinal detachment with choroidal thickening were detected with B-scan ultrasonography. CONCLUSIONS: Our case series demonstrates the uveal characteristics of patients with BDUMP based on high-frequency B-scan ultrasonography and UBM. Ultrasonographic findings are crucial in the diagnosis of BDUMP because it is occult in nature.

Quantitative analysis of retinal and choriocapillary vascular density of multiple evanescent white dot syndrome by optical coherence tomography angiography.

PURPOSE: To describe optical coherence tomography angiography (OCTA) and other multimodal imaging features of multiple evanescent white dot syndrome (MEWDS). METHODS: The retinal and choriocapillary vascular density of MEWDS patients were measured by OCTA (OptoVue Inc.) in the acute and recovery phases. And other multimodal imaging data were also retrospectively reviewed. RESULTS: Sixteen patients with a mean age of 26.5 ± 6.99 years were included. Three patients were complicated with choroidal neovascularization (CNV). The mean baseline logMAR BCVA of the affected eyes was 0.52 ± 0.36 (Snellen equivalent 20/50). OCTA revealed significant reductions in vascular densities of deep capillary plexus (45.72 ± 3.70%, P = 0.0007), and choriocapillaris (46.08 ± 3.22%, P < 0.0001) of the affected eyes compared with the contralateral eyes (50.23 ± 4.06% and 52.28 ± 4.19%, respectively) in the acute phase. During the recovery phases, vascular densities of deep capillary plexus (49.50 ± 3.15%, P < 0.0001) and choriocapillaris (53.67 ± 2.58%, P < 0.0001) increased significantly in the affected eyes while those of the superficial capillary plexus remained stable. SD-OCT revealed an increase of the subfoveal choroidal thickness and disruption of the outer retinal layer, including ellipsoid zone discontinuities and the accumulation of hyperreflective material, corresponding to the hypofluorescent spots and dots on ICGA, respectively. BCVA increased to normal values after recovery, together with restoration of the structural morphology and choroidal thickness on SD-OCT, except in eyes with CNV. CONCLUSION: The inner retinal layer and choroid can be secondarily transiently compromised in MEWDS. MEWDS complicated with CNV is associated with worse visual outcomes.

Optical Coherence Tomography Angiography of Inflammatory Choroidal Neovascularization Early Response after Anti-VEGF Treatment.

Purpose: To describe the optical coherence tomography angiography (OCTA) features of active inflammatory choroidal neovascularization (CNV) and characterize the early responses of anti-vascular endothelial growth factor (VEGF) treatment for inflammatory CNV. Methods: OCT angiography images of inflammatory CNV were acquired and analyzed using the RTVue XR Avanti with AngioVue at baseline as well as fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). OCTA scans were sequentially obtained 1 day before treatment, 1 day, 7 days, 14 days, and 30 days after anti-VEGF injection. Changes of the selected area and flow area of CNV on OCTA were measured along with those of the central macular thickness (CMT) on corresponding SD-OCT. Results: 19 eyes of 18 uveitic patients (mean age: 36.83 ± 10.05 years) presenting with active CNV were included in the prospective case series. The OCTA showed a 100% sensitivity for inflammatory CNV detection in 23 of 23 CNV lesions, revealing prevailing two neovascular phenotypes: vascular loops and intertwined nets. After anti-VEGF injection, as early as the 1-day follow-up, the mean selected area and the mean flow area of inflammatory CNV on OCTA were significantly reduced (both P < .05) while the average CMT on SD-OCT did not change until the 7-day follow-up. OCTA was able to detect the reincrease of capillary density and vessel size predominantly in the second phenotype 14-30 days after anti-VEGF injection. Conclusions: OCTA not only allows for noninvasive detection of inflammatory CNV with a high sensitivity but also facilitates its sequential observation after anti-VEGF treatment. The treatment outcomes are observable at day 1 post treatment. OCTA may be a useful tool for diagnosing inflammatory CNV and evaluating the early response to anti-VEGF treatment.

MicroRNA-29b-3p inhibits cell proliferation and angiogenesis by targeting VEGFA and PDGFB in retinal microvascular endothelial cells.

Purpose: Excessive angiogenesis, also known as neovascularization, has considerable pathophysiologic roles in several retinal diseases, including retinopathy of prematurity, diabetic retinopathy, and exudative age-related macular degeneration. Accumulated evidence has revealed that miRNAs play important roles in endothelial cell dysfunction and angiogenesis. However, the role of microRNA-29b-3p (miR-29b-3p) in retinal angiogenesis is still unclear. Therefore, we investigated whether and how miR-29b-3p affects the function of retinal microvascular endothelial cells (RMECs). Methods: The overexpression and inhibition of miR-29b-3p were achieved by transfecting rat RMECs with an miR-29b-3p mimic and inhibitor, respectively. The proliferation, migration, and angiogenesis of RMECs were evaluated using a Cell Counting Kit-8 assay, Ki67 staining, western blotting (of proliferating cell nuclear antigen, cyclin A2, cyclin D1, and cyclin E1), wound healing test, and tube formation assay. The expression levels of vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB) were examined with quantitative real-time PCR and western blotting, respectively. Results: Overexpression of miR-29b-3p statistically significantly inhibited the function of RMECs in cell proliferation and angiogenesis, while inhibition of miR-29b-3p increased the proliferative and angiogenic activities of RMECs. Moreover, VEGFA and PDGFB, as the targets of miR-29b-3p, were statistically significantly downregulated by the miR-29b mimic, whereas the miR-29b-3p inhibitor had the opposite effects. Conclusions: miR-29b-3p negatively regulates RMEC proliferation and angiogenesis, at least partly by targeting VEGFA and PDGFB. These data may provide a potential therapeutic strategy for treating ocular neovascular diseases.

Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy.

BACKGROUND: Bestrophin-1 (BEST1) gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum of BEST1 in a large cohort of Chinese patients with bestrophinopathy. METHODS: Patients clinically suspected of bestrophinopathy were screened using multigene panel testing. All BEST1 variants were confirmed by Sanger sequencing, and validated in the families. FINDINGS: A total of 92 patients (Best vitelliform macular dystrophy (BVMD)=77; autosomal recessive bestrophinopathy (ARB)=15) from 58 unrelated families of Chinese origin and their available family members (n=65) were recruited. Overall, 39 distinct disease-causing BEST1 variants were identified, including 13 novel variants, and two reported variants but novel for ARB. Of them, 14 were associated with ARB, 23 with BVMD and two (c.604C>T and c.898G>A) with both BVMD and ARB. Most mutations associated with BVMD were missense (97.78%), while ARB was associated with more complex mutations, including missense (88.46%), splicing effect (3.85%), and frameshifts (15.38%). BEST1 hotspots were c.898G>A and c.584C>T among BVMD and ARB patients, respectively. Hot regions were located in exons 8, 2 and 6 in BVMD patients, and in exons 5 and 7 in ARB patients. The overall penetrance of BEST1 in our cohort was 71.30%, no de novo mutations were identified. CONCLUSION: This is the largest study to date that provides major population-based data of the BEST1 mutation spectrum in China. Our results can serve as a well-founded reference for genetic counselling for patients with bestrophinopathy of Chinese origin.