Clinical picture of uveitis in the presence of ocular hypertension and improvement in disease course with dipeptide carnosine

Background: Our previous studies have demonstrated that raised IOP can contribute to an increase in the severity of inflammatory processes in the anterior segment. Given the involvement of free radical processes in the pathogenesis of uveitis, it is reasonable to use antioxidative agents for the treatment of the disease. The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is a highly bioavailable low-molecular hydrophilic antioxidant with a direct effect on certain oxidant species and indirect effect on the system protecting the body from radicals; it contributes to membrane stabilization and can improve inflammatory processes. Purpose: To examine the features of the clinical course of experimental anterior uveitis developing in the presence of ophthalmic hypertension (OHT), and to improve the course with dipeptide carnosine. Material and Methods: Thirty-four rabbits were divided into three groups (group 1, 10 animals with induced allergic uveitis; group 2, 12 animals with OHT induced prior to experimental allergic uveitis; and group 3, 12 animals treated with carnosine for experimental allergic uveitis in the presence of OHT). Animals underwent biomicroscopy, ophthalmoscopy and tonometry. The number of white blood cells (WBC) in the aqueous humor of the anterior chamber was assessed microscopically, and total protein concentration was determined with the Lawry assay. Results: There were significant differences in the conjunctival and scleral injection (р=0.0001), pattern of keratic precipitates (р=0.0009), anterior chamber content (р=0.0034), pattern of posterior synechiae (р=0.0025), vitreous opacity (р=0.0338), and fundus pathology (р=0.0001) between groups of anterior uveitis-only and that with OHT. Even at four weeks of induced anterior uveitis, the number of WBC and the total protein in the aqueous humor of the anterior chamber were 14.3% (p > 0.05) and 27.5%, respectively, higher in in eyes of group 2 compared to eyes of group 1. The course of inflammatory process was significantly more severe in eyes with anterior uveitis in the presence of OHT than in eyes with uveitis-only, based on the comparison in major clinical signs in the anterior and posterior segments. Binocular instillation of carnosine solution in the conjunctival sac for 4 weeks resulted in a significant decrease in the severity of inflammatory process in the anterior and posterior segments in eyes of group 3, leading to an improved clinical picture and restoration of the blood-aqueous barrier and ciliary body transport, with a 45.8% decrease in the WBC and 31.6% decrease in total protein in the aqueous humor of the anterior chamber in treated eyes compared to untreated eyes with induced non-infectious anterior uveitis in the presence of OHT (р < 0.01). Conclusion: Integration of carnosine into the therapeutic regimen for ocular inflammation in the presence of raised IOP would substantially improve treatment outcomes and reduce the complication rate

Ocular hypotensive efficacy of a new liposomal latanoprost formulation administered by different routes for experimental ocular hypertension

Background: Prostaglandin analogs (e.g., latanoprost) are the first-line therapy for glaucoma. These medications, however, have a short antihypertensive effect due to low penetration of topical drug across the corneal epithelium, which causes the need for their daily application for a long time. Therefore, it is clinically and socially important to develop latanoprost medications with improved efficacy against ocular hypertension (OHT) and with improved patient compliance through the prolonged effect of latanoprost. Purpose: To assess (a) changes in intraocular pressure (IOP) with time and (b) duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT. Material and Methods: Twenty-one adult Chinchilla rabbits (age, 1 year; weight, 2.5 to 3.0 kg) were divided into three groups: group 1, animals with induced OHT, which was treated with topical liposomal latanoprost (n = 7); group 2, animals with induced OHT, which was treated with a single subconjunctival injection of liposomal latanoprost (n = 7); and group 3, untreated animals with induced OHT, (n = 7). OHT was induced by two 0.1-mL anterior chamber injections of 0.3% carbomer at 10 day intervals. A 0.1-ml subconjunctival injection of liposomal latanoprost formulation was applied immediately after formation of the model of OHT. Topical liposomal latanoprost (one drop per eye) was bilaterally applied at a dose of 1 drop per eye once daily in the evening. Follow-up duration was 10 weeks. IOP was measured in each group before and after OHT modeling. In addition, it was measured after subconjunctival injection of liposomal latanoprost or first application of topical liposomal latanoprost. Thereafter, IOP measurements were performed once a week. Statistica 5.5 (StatSoft, Tulsa, OK, USA) software was applied for statistical analysis. Non-parametric statistical tests for dependent and independent samples were used. Results: We assessed the pharmacological efficacy and duration of hypotensive effect of a proprietary liposomal latanoprost formulation administered topically or by subconjunctival injection for experimental OHT in rabbits. After OHT modeling was performed, there was a persistent increase in IOP, with the IOP values being 51-65% higher than at baseline (р < 0.001). The IOP in animals with OHT treated daily with topical liposomal latanoprost was 30.5% lower than in untreated animals with OHT (р < 0.001). A single subconjunctival injection of the examined liposomal latanoprost formulation resulted in a 36.7% reduction in IOP compared to baseline (р ˂ 0.001), with the effect being as long as 10 weeks. Conclusion: The current study demonstrated a statistically significant hypotensive effect of topical or subconjunctival injection treatment with the examined liposomal latanoprost formulation, with the effect of a single subconjunctival injection of the formulation being as long as 10 weeks

Effect of experimental type 2 diabetes complicated by pyelonephritis on ltrastructural changes in the choroid, retina and nephrons

Background: The clinical and morphological picture of diabetic microangiopathy is rather specific. Diabetic retinal ischemia can lead to irreversible damage to retinal neural elements and choroidal capillaries. Diabetic nephropathy can lead to progressive renal dysfunction and chronic renal failure. Choroidal and retinal capillaries are structurally and functionally similar to those of the intestinal mucosa and renal tissue. Purpose: To assess vascular ultrastructural changes in the choroid, retina, and renal glomerular and tubular system in a rat model of pyelonephritis in the presence of type 2 diabetes. Material and Methods: Samples were obtained from 95 Wistar rats divided into three groups: group 1 (or control group) of 30 intact animals; group 2 of 15 animals with type 2 diabetes induced by intraperitoneal streptozotocin 15.0 mg/kg for 5 consecutive days; and group 3 of 50 animals with acute pyelonephritis in the presence of type 2 diabetes (streptozotocin 35.0 mg/kg on 2 days spaced by a week). Acute pyelonephritis was induced by Escherichia coli administration (107 CFU/kg) rectally. The ultrastructure of rat choroidal, retinal and renal glomerular-and-tubular vessels was examined with electron microscopy (PEM-100-01 electron microscope). Results: In rats with induced type 2 diabetes, the most significant ocular vascular changes and renal vascular changes were found in endothelial cells. These changes included findings of vacuolar degeneration in some epithelial cells, basal membrane thickening and focal necrosis of individual epithelial cells. Vessel lumens appeared focally narrowed or expanded, with red blood cells forming clumps or sludge in lumens. Some capillaries were obliterated. These changes obviously caused secondary changes in the surrounding structures. Common ocular changes included focal destruction in retinal pigment epithelium cells, destruction of retinal photoreceptor inner segments and choroidal stromal edema. Common renal changes included destruction of the podocytes of the glomerular capillary network and homogenization of the basal membrane. Vascular ultrastructural changes in the renal glomerular system were more marked in rats with experimental type 2 diabetes and pyelonephritis than in those with type 2 diabetes only. Conclusion: Electron microscopy micrographs demonstrated the ultrastructural changes in the retinal and uveal vascular systems which were of a similar type to those in the renal glomerular-and-tubular system in rats with experimental pyelonephritis in the presence of type 2 diabetes

Effect of experimental type 2 diabetes complicated by pyelonephritis on ultrastructural changes in the choroid, retina and nephrons

The clinical and morphological picture of diabetic microangiopathy is rather specific. Diabetic retinal ischemia can lead to irreversible damage to retinal neural elements and choroidal capillaries. Diabetic nephropathy can lead to progressive renal dysfunction and chronic renal failure. Choroidal and retinal capillaries are structurally and functionally similar to those of the intestinal mucosa and renal tissue. Purpose: To assess vascular ultrastructural changes in the choroid, retina, and renal glomerular and tubular system in a rat model of pyelonephritis in the presence of type 2 diabetes. Material and Methods: Samples were obtained from 95 Wistar rats divided into three groups: group 1 (or control group) of 30 intact animals; group 2 of 15 animals with type 2 diabetes induced by intraperitoneal streptozotocin 15.0 mg/ kg for 5 consecutive days; and group 3 of 50 animals with acute pyelonephritis in the presence of type 2 diabetes (streptozotocin 35.0 mg/kg on 2 days spaced by a week). Acute pyelonephritis was induced by Escherichia coli administration (107 CFU/kg) rectally. The ultrastructure of rat choroidal, retinal and renal glomerular-and-tubular vessels was examined with electron microscopy (PEM- 100-01 electron microscope). Results: In rats with induced type 2 diabetes, the most significant ocular vascular changes and renal vascular changes were found in endothelial cells. These changes included findings of vacuolar degeneration in some epithelial cells, basal membrane thickening and focal necrosis of individual epithelial cells. Vessel lumens appeared focally narrowed or expanded, with red blood cells forming clumps or sludge in lumens. Some capillaries were obliterated. These changes obviously caused secondary changes in the surrounding structures. Common ocular changes included focal destruction in retinal pigment epithelium cells, destruction of retinal photoreceptor inner segments and choroidal stromal edema. Common renal changes included destruction of the podocytes of the glomerular capillary network and homogenization of the basal membrane. Vascular ultrastructural changes in the renal glomerular system were more marked in rats with experimental type 2 diabetes and pyelonephritis than in those with type 2 diabetes only. Conclusion: Electron microscopy micrographs demonstrated the ultrastructural changes in the retinal and uveal vascular systems which were of a similar type to those in the renal glomerular-and-tubular system in rats with experimental pyelonephritis in the presence of type 2 diabetes