Inhibition of Aldose Reductase by Novel Phytocompounds: A Heuristic Approach to Treating Diabetic Retinopathy.

Aldose reductase (ALR2) activation in the polyol pathway has been implicated as the primary mechanism for the progression of diabetic retinopathy. Most of the aldose reductase inhibitors (ARIs), used for the treatment of diabetic complications, were withdrawn due to ineffective treatment and adverse side effects caused by nonspecificity. Epalrestat, a carboxylic acid inhibitor, is the only ARI used for the treatment of diabetic neuropathy, though associated with minor side effects to 8% of the treated population. Our study exploited the interactions of Epalrestat-ALR2 crystal structure for the identification of specific phytocompounds that could inhibit human lens ALR2. 3D structures of plant compounds possessing antidiabetic property were retrieved from PubChem database for inhibition analysis, against human lens ALR2. Among the shortlisted compounds, Agnuside and Eupalitin-3-O-galactoside inhibited lens ALR2 with IC50 values of 22.4 nM and 27.3 nM, respectively, compared to the drug Epalrestat (98 nM), indicating high potency of these compounds as ALR2 inhibitors. IC50 concentration of the identified ARIs was validated in vitro using ARPE-19 cells. The in silico and in vitro approaches employed to identify and validate specific and potent ALR2 inhibitors resulted in the identification of phytocompounds with potency equal to or better than the ALR2 inhibiting drug, Epalrestat.

Incidence and risk factors for postoperative intraocular pressure response to topical prednisolone eye drops in patients undergoing phacoemulsification.

AIM/PURPOSE: To report the incidence, risk factors, and magnitude of steroid response in individuals receiving topical 1% prednisolone acetate eye drops following phacoemulsification surgery MATERIALS AND METHODS: Postoperative IOP of 1118 consecutive patients who had uneventful cataract surgery and used 1% topical prednisolone acetate were studied. Baseline ocular parameters like best-corrected visual acuity, IOP, and slit-lamp examination findings were noted preoperatively and at postoperative day 30. Incidence of postoperative intraocular pressure response to steroid was analyzed and graded as mild, moderate, or severe and risk factors studied. RESULTS: The mean age of our study cohort was 59.49 ± 7.25 years. The overall incidence of steroid response was 3.2%, (2.8% being moderate responders, and 0.4% high responders). Mean preoperative IOP was 14.67 ± 2.2 mm Hg in the study cohort (n = 1118). Mean postoperative IOP was 21.33 ± 7.97 mm Hg in the steroid responder (SR) and 14.66 ± 2.8 mm Hg in the non-responder (NR), with a statistically significant difference from the baseline IOP in the SR group (p < 0.001) and no difference in the NR. Univariate analysis revealed younger age and high axial length as risk factors but on multiple regression analysis, only younger age < 50 years was found to be a significant risk factor for steroid response. CONCLUSION: The overall steroid response in this population post-cataract surgery was low with most being moderate responders. Younger age and higher axial length were identified as risk factors for steroid response, and hence this warrants the judicious use of steroids in such individuals.

In Vitro Evaluation of the Drug Reservoir Function of Human Amniotic Membrane Using Moxifloxacin as a Model Drug.

PURPOSE: To evaluate the in vitro, extended drug reservoir function of human amniotic membrane (HAM) of different thicknesses impregnated with moxifloxacin. METHODS: HAM buttons (12 mm) were soaked with freshly prepared 0.5% wt/vol topical moxifloxacin at different soaking time intervals: 3 hours (group I), 6 hours (group II), 12 hours (group III), 24 hours (group IV), and 48 hours (group V). They were then transferred into 1 mL of fresh simulated tear fluid (pH-7.4) and incubated at 37°C. The release kinetics of moxifloxacin was studied by analyzing the amount of drug in simulated tear fluid collected at different time intervals from each pretreated HAM for 3 weeks. In another experiment, thin and thick HAMs were selected based on weight and soaked with moxifloxacin for 24 hours, and the release kinetics was studied for 7 weeks. All samples were stored at -80°C until analysis by high-performance liquid chromatography. RESULTS: No significant difference was observed between different soaking times and the release of moxifloxacin. The cumulative amount of moxifloxacin released from thick HAM was found to be statistically significant compared with thin HAM (P < 0.05). CONCLUSIONS: Our in vitro data showed that the sustained release of moxifloxacin from HAM was achieved up to 7 weeks. The entrapment efficiency of moxifloxacin was significantly higher in thicker HAM than in thin HAM. Moxifloxacin-impregnated HAM application can be considered in bacterial keratitis to provide sustained drug delivery through a biological bandage system for up to a period of 7 weeks.