Brinzolamide-induced retinopathy in neonatal rats: an alternative animal model of retinal neovascularization

Background and Purpose: Neovascular retinal pathology is steel uncertain. Thus, there is great need to investigate new modeling, diagnostic and treatment technologies. Brinzolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss). In the present study the influence of brinzolamide-induced acidosis on preretinal neovascularization in neonatal rat was investigated. Materials and Methods. In our study we used newborn Wistar rats raised in two litters. Newborn rats (n=17) were randomized to either intraperitoneal brinzolamide in dose 200 mg/kg (n=9) or saline (n=8), twice daily from days 2 to 7. After 5 days of recovery all rats were euthanized. Six paraffin-embedded sections prepared in a standard manner and stained with hematoxylin and eosin. To investigate the damage, we evaluated the number of cells in the ganglion cell layer (GCL) and the thicknesses of the inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL). The cells in GCL and the thicknesses of the IPL, INL, and ONL at a distance between 375 and 625 μm from the optic disc were measured. Results: Preretinal neovascularization was found in 71% retinas, from brinzolamide-injected rats. Cataract formation was detected in 100% eyes after brinzolamide injections. All retinas from saline group were negative for neither neovascularization nor cataract. Brinzolamide rat model retinas showed decrease in the thicknesses of the retinal layers. Conclusion: In the present study, we report that brinzolamide (a drug causing metabolic acidosis primarily by bicarbonate loss) is associated with preretinal neovascularization in the neonatal rat. So this method can be suitable model for other neovascular pathologies of the eye

Investigating the protective capacity of polymethylsiloxane polyhydrate against chromium (VI)-induced neurotoxicity of the rat optic nerve

Background: Toxic optic neuropathy commonly develops in the presence of exogenous factors. With progression of the process, acute or chronic progressive death of retinal ganglion cells and their axons develops, leading to partial or total optic atrophy with visual function loss. Investigation of the effect of chromium (VI) on the optic nerve and evaluation of potential pathogenetic treatments of this effect are deemed relevant because of the global environmental crisis associated with pollution from chromium. Purpose: To examine chromium (VI)-induced morphological changes in the rat optic nerve and to experimentally assess the efficacy of polymethylsiloxane polyhydrate (PMSPH) for correction of induced changes. Material and Methods: Seventy two white outbred adult male rats were distributed in three groups (24 animals each) given water ad libitum. Animals in group 1 (a control group) were intact and given normal drinking water. Those in group 2 were given chromium (VI) (K2Cr2O7)-enriched (0.02 mol/L) drinking water but not Enterosgel. Animals in group 3 were given K2Cr2O7-enriched (0.02 mol/L) drinking water and treated with oral Enterosgel (0.8 mg/kg). Animals were decapitated under ether anesthesia and the intracranial optic nerve was harvested at three time points (20, 40 and 60 days after initiation of the experiment), and changes in the optic nerve were assessed by histomorphology and electron microscopy. Results: Histomorphology found disrupted and fragmented nerve fibers, edematous connective tissue septa, and diffuse cellular gliosis in day-60 intracranial optic nerve specimens obtained from animals given chromium (VI)-enriched drinking water and not treated with Enterosgel. In addition, there was scanning electron microscopy evidence of electrolyte disbalance and accumulation of chromium (VI). Treatment with Enterosgel completely inhibited the effect of chromium (VI) on the rat optic nerve at days 20 and 40, and we observed only minimal consequences of discirculatory changes in day-60 specimens obtained from animals given chromium (VI)-enriched drinking water and treated with Enterosgel

Aberrant overexpression of membrane-associated mucin contributes to tumor progression in adult T-cell leukemia/lymphoma cells.

Aberrant overexpression of membrane-associated mucin (MUC1) is implicated in the pathogenesis of cancer, particularly of adenocarcinomas. Adult T-cell leukemia/lymphoma (ATL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), exhibits invasive tropism into various organs, resulting in disease progression and resistance to treatment. In the present study, we showed that MUC1 is overexpressed exclusively in cells of ATL among hematological malignancies. Furthermore, increased expression of MUC1 correlated with a poor prognosis, suggesting MUC1 to be a prognostic marker in ATL. Various functional analyses with knockdown experiments using a specific siRNA for MUC1 revealed that MUC1 is involved in cell growth, cell aggregation, and resistance to apoptosis. Although it has been shown that the anti-adhesive properties of MUC1 facilitate migration and metastasis of tumor cells, our findings indicated that MUC1 contributes to cell-cell adhesion. Mucins thus seem to play a role in the pathogenesis and/or progression of ATL

Патоморфологічні аспекти застосування ядровмісних клітин кордової крові при неоваскулярній ретинопатії у експериментальних щурів

The effect of cord blood derived nuclear cells on neovascular retinopathy in experimental rats was studied. Regression of neovascular tissue, retinal structure normalization was found after 45 day post single intravitreal injection of cord blood derived nuclear cells.В экспериментальной работе изучалось действие препарата криоконсервированной кордовой крови на сетчатую оболочку крыс с моделированной неоваскулярной ретинопатией. Установлено, что на 45-ые сутки после однократного интравитреального введения ядросодержащих клеток пуповинной крови происходит обратное развитие новообразованных сосудов и нормализация архитектоники сетчатой оболочки.В експериментальній роботі вивчалася дія препарату кріоконсервованої кордової крові на сітківку щурів із модельованою неоваскулярною ретинопатією. Встановлено, що на 45-ту добу після одноразового інтравітреального уведення ядровмісних клітин кордової крові відбувається зворотний розвиток новоутворених судин і нормалізація архітектоніки сітківки

Eye retinal changes under the influence of chromium ions

Introduction. Relationships between human eyes and metal ions take multiple forms. Neurotoxicity manifests as peripheral neuropathy, sensorineural hearing loss; ocular toxicity is presented as visual impairment. Regulation of heavy metal toxicity by the heat shock proteins (HSP90) and S100 family proteins has not been investigated in eye retina. The aim of our study was to investigate S100 and HSP90 expression in retina under the influence of chromium ion. Material and Methods. 36 (72 eyes) male albino rats that weighed 300-325 g were evaluated for histological and immunostainings for HSP90aa1 and S100. 18 rats of experimental group (36 eyes) got potassium bichromate (Sigma, USA) into drinking water in a dose of 0.02 mol/l. The rats of control group (18 individuals) drank usual drinking water. Animals were taken out of experiment at Days 20, 40 and 60 (first, second and third groups, respectively, six animals in each group) after the beginning of potassium bichromate introduction. Results. We noted the HSP90aa1 enzymatic activity in the control group. Induction of the enzymatic activity of HSP90aa1 was increased in the second group (89.7±3.5% P<0.05). S100 was expressed in the control 5.24±0.58% and experimental groups (first group - 5.67±0.32%, P˃0.05; second group - 25.72±1.54% P<0.05; third group - 34.14±2.54%, P<0.05). Conclusion. Our data conclude that HSP90aa1 and S100 proteins functionally interact during the regulation of retinal cells under the influence of chromium ion. Chromium is toxic heavy metal that has led to retinal edema. It plays a major role in retinopathy development. The potential of Chromium ion toxicity and its possible role in causing diseases of retina requires further study