Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia.

Choroidal atrophy is a common fundus pathological change closely related to the development of age-related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC-ECs) through the MESP1+ mesodermal progenitor stage express CECs-specific markers and can integrate into choriocapillaris. Single-cell RNA-seq (scRNA-seq) studies show that hPSC-ECs upregulate angiogenesis and immune-modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC-ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close-up examination shows that engrafted hPSC-ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC-ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.

Bruch's-Mimetic Nanofibrous Membranes Functionalized with the Integrin-Binding Peptides as a Promising Approach for Human Retinal Pigment Epithelium Cell Transplantation.

BACKGROUND: This study aimed to develop an ultrathin nanofibrous membrane able to, firstly, mimic the natural fibrous architecture of human Bruch's membrane (BM) and, secondly, promote survival of retinal pigment epithelial (RPE) cells after surface functionalization of fibrous membranes. METHODS: Integrin-binding peptides (IBPs) that specifically interact with appropriate adhesion receptors on RPEs were immobilized on Bruch's-mimetic membranes to promote coverage of RPEs. Surface morphologies, Fourier-transform infrared spectroscopy spectra, contact angle analysis, Alamar Blue assay, live/dead assay, immunofluorescence staining, and scanning electron microscopy were used to evaluate the outcome. RESULTS: Results showed that coated membranes maintained the original morphology of nanofibers. After coating with IBPs, the water contact angle of the membrane surfaces varied from 92.38 ± 0.67 degrees to 20.16 ± 0.81 degrees. RPE cells seeded on IBP-coated membranes showed the highest viability at all time points (Day 1, p < 0.05; Day 3, p < 0.01; Days 7 and 14, p < 0.001). The proliferation rate of RPE cells on uncoated poly(ε-caprolactone) (PCL) membranes was significantly lower than that of IBP-coated membranes (p < 0.001). SEM images showed a well-organized hexa/polygonal monolayer of RPE cells on IBP-coated membranes. RPE cells proliferated rapidly, contacted, and became confluent. RPE cells formed a tight adhesion with nanofibers under high-magnification SEM. Our findings confirmed that the IBP-coated PCL membrane improved the attachment, proliferation, and viability of RPE cells. In addition, in this study, we used serum-free culture for RPE cells and short IBPs without immunogenicity to prevent graft rejection and immunogenicity during transplantation. CONCLUSIONS: These results indicated that the biomimic BM-IBP-RPE nanofibrous graft might be a new, practicable approach to increase the success rate of RPE cell transplantation.

[Association of choroidal thickness with diabetic retinopathy at different stages].

OBJECTIVE: To explore the association of choroidal thickness variations in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) at different stages. METHODS: A total of 161 patients with T2DM were included in this study, from October 2012 to June 2014. According to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, the patients were divided into 5 groups: non-DR without diabetic macular edema (DME) group(DR-/DME- group, 45 eyes), nonproliferative diabetic retinopathy (NPDR) without DME group(NPDR+/DME- group, 58 eyes), proliferative diabetic retinopathy (PDR) without DME group (PDR+/DME- group, 12 eyes), NPDR with DME group (NPDR+/DME+ group, 41 eyes), PDR with DME group (PDR+/DME+ group, 5 eyes). Meanwhile, 60 normal subjects were enrolled as the control group. All study subjects received optical coherence tomography enhanced depth imaging (EDI-OCT) examination to detect and compare subfoveal choroidal thickness at different stages of DR. RESULTS: Mean SFCT was (271 ± 36), (270 ± 35), (262 ± 38), (244 ± 36), (229 ± 35) µm respectively in control, DR-/DME-, NPDR+/DME-, PDR+/DME-, NPDR+/DME+ groups. The SFCTs of PDR+/DME- and NPDR+/DME+ group were statistically lower than that of control group (P=0.004, P=0.001). The SFCT of PDR+/DME- group was lower than that of DR-/DME- group (P=0.003), and there was also a significant difference of SFCT between NPDR+/DME+ and NPDR+/DME- group (P=0.001). There was linear correlation between SFCT and the logMAR best-corrected visual acuity (r=0.397, P<0.01), but the SFCT was independent of diabetic duration, fasting blood glucose, HbA1c, axial length, diastolic blood pressure (DBP) and systolic blood pressure SBP (r=-0.024, 0.159, 0.089, 0.036, 0.143, 0.057, all P>0.05). There was no significant difference of SFCT among different DME types (F=0.071, P>0.05). CONCLUSION: The SFCT decreased with increasing severity of DR. To monitor the SFCT in T2DM patients may be helpful to evaluate the severity of DR and provide a new treatment conception.

Urinary albumin excretion rate: a risk factor for retinal hard exudates in macular region in type 2 diabetic patients.

BACKGROUND: The various risk factors for retinal hard exudates are still poorly understood in type 2 diabetic patients. The aim of this study was to determine the association between urinary albumin excretion rate (UAER) and hard exudates in macular region in north Chinese patients. METHODS: A total of 272 patients (272 eyes) were enrolled for this study, including 154 subjects from group 1 (mild hard exudates), 91 subjects from group 2 (moderate hard exudates) and 27 subjects from group 3 (severe hard exudates) confirmed using colour fundus photography, optical coherence tomography (OCT) as well as slit-lamp biomicroscopy with 78 diopter (D) lens. Each participant underwent a comprehensive assessment that included biochemical, clinical characteristics test and detailed ophthalmic evaluation. One-way analysis of variance (ANOVA) test and chi-square test were performed to analyze the fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), full blood counts, urinary albumin excretion rate (UAER), blood creatinine (CREA), duration of diabetes, body mass index (BMI), systolic blood pressures (SBP) and diastolic blood pressures (DBP) between groups. Ordinal logistic regression analysis was further performed in order to eliminating the possible confounding factors. RESULTS: Three groups were matched in terms of age and gender. Risk factors which showed significant difference between groups include FBG (P < 0.001), HbA1c (P < 0.001), LDL (P < 0.001), UAER (P < 0.001), duration of diabetes (P = 0.001), TC (P = 0.005), SBP (P = 0.026), CREA (P = 0.004) and haemoglobin (Hb) (P = 0.012). There was no significant difference between groups for the TG, HDL, DBP, platelet, total white blood cells and BMI. Using ordinal Logistic regression analyses, of all the variables, HbA1c, LDL and UAER which were independent risk factor for hard exudates showed a significantly odds ratio of 1.25, 3.07, and 1.39, respectively. There were also significant differences in UAER level between patients with mild, moderate, severe hard exudates groups (P < 0.001). CONCLUSIONS: UAER was an independent risk factor associated with retinal hard exudates in macular region in type 2 diabetic patients. This study highlights the need for close monitoring and fundus examination for hard exudates in patients with elevated UAER to prevent irreversible visual loss.