Effects of 4-phenylbutyric acid on the development of diabetic retinopathy in diabetic rats: regulation of endoplasmic reticulum stress-oxidative activation.

There are good evidences suggesting that endoplasmic reticulum (ER) stress can be one of the contributing factors in the development of diabetic retinopathy. The present study was designed to investigate the effect of chemical chaperone 4-phenylbutyric acid (4-PBA) in alleviating the ER stress, and diabetic retinopathy in type 2 diabetic rats. Treatment of diabetic rats with 4-PBA, increased the antioxidant capacity, reduced the levels of lipid peroxidation, organised the state of apoptosis and regulated the ER stress - oxidative activation in retinal tissue. Also there was an improvement in the histological picture of retinal specimens compared to untreated diabetic rats. It was concluded that 4-PBA is a promising therapeutic agent for ER stress diseases such as diabetic retinopathy.

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin-induced diabetic cataract in rats.

The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase-12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS-PAGE and UV absorption while changes in lenticular α-crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T-AOC, MDA, H2 O2 , and caspase-12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA-treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA-treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.

Refinement of Intraocular Pressure Measurements made by Ocular Response Analyzer following Laser in Situ Keratomileusis using M2 90 Moria Microkeratome for Egyptian Myopic and Astigmatic Patients.

INTRODUCTION: The Goldmann applanation tonometer readings were noted to be markedly reduced after Lasik surgery using a thin flap technique which is widely used nowadays, to correct a wide range of myopia and astigmatism. The Ocular Response Analyzer (ORA) is considered one of the important tools for refinement of Intraocular Pressure (IOP) measurements. The aim of this study is to evaluate and refine ORA measurements for IOP changes post- M2 90 Moria microkeratome Lasik procedure for Egyptian myopic and astigmatic patients trying to aid in glaucoma diagnosis and management. METHODS: Thirty-five eyes of nineteen Egyptian patients with myopia or myopic astigmatism who had undergone Lasik procedure using M2 90 Moria microkeratome were included in this consecutive case series study. All cases were subjected to full ophthalmological examination including uncorrected and best corrected visual acuity, refraction, slit lamp examination, Scheimpflug imaging and ORA (Reichert Ophthalmic Instruments, Inc., Buffalo, NY, USA). The refractive errors were measured using an auto refractometer and were confirmed by trial. For the ocular response analyzer, the Goldmann-correlated IOP measurement (IOPg) which simulates IOP measured by Goldmann tonometer and the Corneal-Compensated Intraocular Pressure (IOPcc) that takes corneal biomechanical properties into consideration were reported as well as the Corneal Hysteresis (CH) and the Corneal Resistance Factor (CRF). Cases were examined preoperatively and again about one month after Lasik, after stabilization of eye condition. The collected data were tabulated and analysed with the suitable statistical methods. The mean values and standard deviation were calculated for quantitative data. Comparison tests (t-test) and correlation tests (Pearson) were also performed. RESULTS: In our study, involving M2 90 Moria microkeratome Lasik procedure, a highly significant post-Lasik reduction in IOPg (t-test = 8.62 (p<0.01), and a statistically significant reduction in IOPcc (t-test = 3.37 (p<0.05) by ocular response analyzer. The average post-Lasik reduction in IOP in mmHg was 4.84±2.82 for IOPg and 2.23±3.51for IOPcc. A statistically significant correlation (p<0.05) existed between post-Lasik reduction of IOPg and ablation depth as well as preoperative spherical equivalent. A non-significant correlation existed between post-Lasik reduction of IOPcc and both of ablation depth and preoperative spherical equivalent. CONCLUSIONS: Following Lasik procedure using M2 90 Moria microkeratome, the IOPcc values by ORA were closer to the preoperative values than the IOPg values and the reduction of IOPcc values was not affected by ablation depth (i.e. preoperative spherical equivalent). Therefore, it is advisable to use the IOPcc values by ORA when evaluating post-Lasik patients for glaucoma diagnosis and management, but with the addition of the average value for post-Lasik reduction which in the study was 2.23±3.51mmHg.