Protective Effect of Pemafibrate Treatment against Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats.

Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.

Pathological Features of Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats.

OBJECTIVE: The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal. METHODS: The eyes of SDT fatty, SDT (controls), and Sprague Dawley (SD) rats (normal controls) were enucleated at 8, 16, 24, 32, and 40 weeks of age (n = 5-6 for each rat type at each age). The retinal thicknesses, numbers of retinal folds, and choroidal thicknesses were evaluated. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using a cell-counting algorithm. RESULTS: The retinas tended to be thicker in the SDT fatty rats and SDT rats than in the SD rats; the choroids tended to be thicker in the SDT fatty rats than in the SD rats. The retinal folds in the SDT fatty rats developed earlier and were more severe than in the SDT rats. Quantitative analyses showed that the GFAP- and VEGF-positive regions in the retinas of the SDT fatty rats were significantly larger than those of the SDT rats. CONCLUSIONS: SDT fatty rats developed more severe DR earlier than the SDT rats. The SDT fatty rats might be useful as a type 2 diabetes animal model to study DR.

Diabetic Retinal and Choroidal Edema in SDT Rats.

We evaluated the features of diabetic retinal and choroidal edema in Spontaneously Diabetic Torii (SDT) rats. We measured the retinal and choroidal thicknesses in normal Sprague-Dawley (SD) rats (n = 9) and SDT rats (n = 8). The eyes were enucleated 40 weeks later after they were diagnosed with diabetes, and 4-micron sections were cut for conventional histopathologic studies. The mean retinal and choroidal thicknesses were significantly thicker in the SDT rats than in the normal SD rats. The choroidal thickness was correlated strongly with the retinal thickness in both rat models. Diabetic retinopathy (DR) and diabetic choroidopathy appeared as edema in the SDT rats. The retinal thickness was correlated strongly with the choroidal thickness in the SDT rats, which is an ideal animal model of both DR and choroidopathy.

Relationship between variations in posterior vitreous detachment and visual prognosis in idiopathic epiretinal membranes.

PURPOSE: To clarify the relationship between variations in posterior vitreous detachments (PVDs) and visual prognoses in idiopathic epiretinal membranes (ERMs). METHODS: In this retrospective, observational, and consecutive case series, we observed variations in PVDs in 37 patients (mean age, 65.7±11.0 years) with ERMs and followed them for 2 years. Three PVD types were found biomicroscopically: no PVD, complete PVD with collapse (C-PVD with collapse), and partial PVD without shrinkage, with persistent vitreous attachment to the macula through the premacular hole of the posterior hyaloid membrane (P-PVD without shrinkage [M]). The best-corrected visual acuity (BCVA) was measured and converted to the logarithm of the minimum angle of resolution (logMAR) BCVA at the first visit and 2 years later. RESULTS: No PVD was observed in 16 of the 37 eyes (mean age, 61.3±11.3 years), C-PVD with collapse in 11 of the 37 eyes (mean age, 69.1±9.9 years), and P-PVD without shrinkage (M) in 10 of the 37 eyes (mean age, 69.3±10.9 years). The logMAR BCVA at the first visit was the worst in the P-PVD without shrinkage (M) group (0.22±0.35) compared with the no-PVD group (-0.019±0.07; P<0.01) and the C-PVD group (0.029±0.08; P<0.05). The logMAR BCVA 2 years later was also worst in the P-PVD without shrinkage (M) group (0.39±0.35) compared with the no-PVD group (0.04±0.13) and the C-PVD with collapse group (0.03±0.09; P<0.05 for both comparisons). The change in the logMAR BCVA over the 2-year follow-up period was worst in the P-PVD without shrinkage (M) group (0.17±0.23) compared with the no-PVD group (0.06±0.14) and the C-PVD with collapse group (0.0009±0.09; P<0.05 for both comparisons). CONCLUSION: Cases with an ERM with a P-PVD without shrinkage (M) had a worse visual prognosis than those with an ERM with no PVD and C-PVD with collapse.

Effect of ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats.

PURPOSE: To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats. METHODS: The animals were divided into six groups, normal Sprague-Dawley rats (n = 8), untreated SDT rats (n = 9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day, n = 7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day, n = 7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured. RESULTS: The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP. CONCLUSION: Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

How good is transplantation of corneal parts compared with penetrating keratoplasty?

The concept of transplantation of corneal parts is to replace only diseased tissues, while leaving healthy host tissues intact. Advantages of the new surgical approaches include fast recovery, resistance to trauma, and less postoperative complications. Despite the theoretical benefits, however, only few data are available in terms of the pros and cons of the new surgical methods. In this review, we analyzed our data on deep anterior lamellar keratoplasty (DALK) and Descemet stripping automated endothelial keratoplasty (DSAEK). Difficulty of surgical procedure still remains in DALK, and intraoperative Descemet membrane (DM) rupture is a major concern. We recently introduced a new DM exposure technique: the double-bubble method. We also investigated the influence of DM rupture on graft survival and visual function. Other concerns in DALK are long-term stability of endothelial density and interface opacity. We also investigated safety and efficacy of subsequent cataract surgery and found that the surgery can be performed safely without significant intraoperative complications. Visual improvement was excellent, and endothelial density remained stable. Although recent increase of DSAEK is remarkable, refinements in surgical procedure are needed, especially in Asian small eyes. Recent developments in surgical technique and instruments in graft insertion are presented. DSAEK is advantageous in the management of postoperative complications, including suture-associated troubles, astigmatism, and epithelial damage. However, we encounter new complication such as graft dislocation. Surgical outcomes of our series and those of other institutes are discussed.