ABSTRACT
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia. The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]-4-(hydroxymethyl)-7-[[(4-methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81±2.71 area%; HG: 14.29±4.30 area%; HG+XNT: 26.87±1.86 area%; P<0.05). Importantly, ACE2 activation significantly increased the RCG number in comparison with HG animals (control: 553.5±14.29; HG: 530.8±10.3 cells; HG+XNT: 575.3±16.5 cells; P<0.05). This effect was accompanied by a reduction in the expression of caspase-3 in RGC of the HG+XNT group when compared with untreated HG rats (control: 18.74±1.59; HG: 38.39±3.39 area%; HG+XNT: 27.83±2.80 area%; P<0.05). Treatment with XNT did not alter the VEGF expression in HG animals (P>0.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats.
Subject(s)
Animals , Male , Hyperglycemia/complications , Peptidyl-Dipeptidase A/metabolism , Retinal Diseases/etiology , Retinal Diseases/prevention & control , Secondary Prevention/methods , Administration, Oral , Apoptosis , /metabolism , Cell Proliferation/physiology , Cell Survival/physiology , Diabetes Mellitus, Experimental/metabolism , Enzyme Activation , Hyperglycemia/chemically induced , Immunohistochemistry , Peptidyl-Dipeptidase A/drug effects , Rats, Wistar , Retinal Diseases/metabolism , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Streptozocin , Vascular Endothelial Growth Factor A/metabolism , Xanthones/administration & dosageABSTRACT
Massive retinal gliosis (MRG) is a rare, benign intraocular condition that results from the proliferation of well-differentiated glial cells. Immunohistochemically, these cells show positivity for glial fibrillary acid protein (GFAP), neuron specific enolase (NSE), and S-100 protein. We encountered a case of a 45-year-old female with loss of vision in the left eye. She had a history of trauma to that eye two years ago. Enucleation was carried out, because malignancy was suspected due to retinal calcification. On the basis of light microscopy and immunohistochemistry (IHC) performed on the enucleated eye, it was diagnosed as massive retinal gliosis.
Subject(s)
Blindness/etiology , Blindness/surgery , Eye Enucleation , Female , Glial Fibrillary Acidic Protein/metabolism , Gliosis/complications , Gliosis/diagnosis , Gliosis/metabolism , Gliosis/physiopathology , Humans , Immunohistochemistry , Middle Aged , Phosphopyruvate Hydratase/metabolism , Retinal Diseases/complications , Retinal Diseases/diagnosis , Retinal Diseases/metabolism , Retinal Diseases/physiopathology , S100 Proteins/metabolism , Severity of Illness Index , Tomography, X-Ray Computed , Vision, MonocularABSTRACT
PURPOSE: To measure the concentrations of iron, copper and zinc in human vitreous and to interpret their levels with various vitreoretinal diseases like proliferative diabetic retinopathy, retinal detachment, intraocular foreign body, Eales' disease and macular hole. METHODS: Undiluted vitreous fluid collected during pars plana vitrectomy was used to measure trace elements using an atomic absorption spectrophotometer. RESULTS: The level of vitreous iron increased threefold in Eales' disease (1.85 +/- 0.36 pg/ml), 2.5-fold in proliferative diabetic retinopathy (1.534 +/- 0.17 pg/ml) and 2.3-fold in eyes with intraocular foreign body (1.341 +/- 0.25 pg/ml) when compared with macular hole (0.588 +/- 0.16 pg/ml). This was statistically significant (P < 0.05). Zinc was found to be low in Eales' disease (0.57 +/- 0.22 pg/ ml) when compared with other groups, though the difference was not statistically significant. CONCLUSION: The increased level of iron with decreased zinc content in Eales' disease confirms the earlier reported oxidative stress mechanism for the disease. In proliferative diabetic retinopathy and intraocular foreign body the level of iron increases. This is undesirable as iron can augment glycoxidation, which can lead to increased susceptibility to oxidative damage, in turn causing vitreous liquefaction, posterior vitreous detachment and ultimately retinal detachment and vision loss.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Copper/metabolism , Eye Diseases/metabolism , Female , Humans , Iron/metabolism , Male , Middle Aged , Oxidative Stress , Retinal Diseases/metabolism , Spectrophotometry, Atomic , Vitrectomy , Vitreous Body/metabolism , Zinc/metabolismABSTRACT
To understand the pathogenesis of proliferative vitreoretinal membrane formation which occurs in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), etc., accurate identification of the cellular components of the membrane is needed. This study was performed to identify cellular components of the membranes by means of immunohistochemical technique. 11 proliferative vitreoretinal membranes which were surgically obtained from 7 eyes with PVR and 4 eyes with PDR were stained with monoclonal antibodies against cytokeratin, glial fibrillary acidic protein (GFAP), or vimentin using immunoperoxidase technique (ABC method). In the PVR membranes, mean cell positivities for cytokeratin, GFAP and vimentin were 48%, 1% and 92%, respectively and in the PDR membranes, 0%, 5% and 93%, respectively. The above results suggest that retinal pigment epithelial cells and fibroblasts are major cellular components of PVR membranes, and that mesenchymal cells are major cellular components and glial cells are minor cellular components of PDR membranes.