Dataset Information

Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines.

ABSTRACT: We developed and characterized a canine model of outer retinal degeneration induced by sodium iodate (SI) intravitreal injection after vitrectomy. In the preliminary study, we repeatedly injected SI intravitreally into the eyes of three canines to develop outer retinal degeneration two weeks after vitrectomy. Based on the preliminary study, a single dose of either 1.2?mg or 1.0?mg SI/0.05?mL was also injected (1.2?mg?in n?=?5 canines, 1.0?mg?in n?=?2 canines). Spectral domain-optical coherence tomography (OCT), electroretinography (ERG), and histological examinations were performed at baseline and following intravitreal injection. In the preliminary study, after a 0.5-mg SI injection and a 1.0-mg SI injection and after two 0.8-mg SI injections, retinal degeneration with retinal thinning was observed on OCT imaging. In the second study, after a single 1.0- or 1.2-mg SI injection, outer retinal degeneration was induced. All eyes showed diffuse outer retinal degeneration on OCT and a loss of both cone and rod responses in ERG. Histological examination also showed the loss of outer retinal layer. Intravitreally injected SI (1.0-1.2?mg) in a vitrectomized canine model induced outer retinal degeneration effectively, and could be evaluated through in vivo ophthalmic examination.

SUBMITTER: Ahn SM

PROVIDER: S-EPMC7046695 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines.

Ahn So Min SM Ahn Jungryul J Cha Seongkwang S Yun Cheolmin C Park Tae Kwann TK Kim Young-Jin YJ Goo Yong Sook YS Kim Seong-Woo SW

Scientific reports 20200227 1

We developed and characterized a canine model of outer retinal degeneration induced by sodium iodate (SI) intravitreal injection after vitrectomy. In the preliminary study, we repeatedly injected SI intravitreally into the eyes of three canines to develop outer retinal degeneration two weeks after vitrectomy. Based on the preliminary study, a single dose of either 1.2 mg or 1.0 mg SI/0.05 mL was also injected (1.2 mg in n = 5 canines, 1.0 mg in n = 2 canines). Spectral domain-optical coherence t ...[more]

PMID: 32107442

Similar Datasets

Project description:ObjectiveTo assess the electrophysiologic, histologic, and biochemical features of an animal model of Smith-Lemli-Opitz syndrome (SLOS).MethodsSprague-Dawley rats were treated with AY9944, a selective inhibitor of 3beta-hydroxysterol-Delta(7)-reductase (the affected enzyme in SLOS). Dark- and light-adapted electroretinograms were obtained from treated and control animals. From each animal, 1 retina was analyzed by microscopy, and the contralateral retina plus serum samples were analyzed for sterol composition. The main outcome measures were rod and cone electroretinographic amplitudes and implicit times, outer nuclear layer (ONL) thickness, rod outer segment length, pyknotic ONL nucleus counts, and the 7-dehydrocholesterol/cholesterol mole ratio in the retina and serum.ResultsBy 10 weeks' postnatal age, rod and cone electroretinographic wave amplitudes in AY9944-treated animals were significantly reduced and implicit times were significantly increased relative to controls. Maximal rod photoresponse and gain values were reduced approximately 2-fold in treated animals relative to controls. The ONL thickness and average rod outer segment length were reduced by approximately 18% and 33%, respectively, and ONL pyknotic nucleus counts were approximately 4.5-fold greater in treated animals relative to controls. The retinal pigment epithelium of treated animals contained massive amounts of membranous/lipid inclusions not routinely observed in controls. The 7-dehydrocholesterol/cholesterol mole ratios in treated retinas and serum samples were approximately 5:1 and 9:1, respectively, whereas the ratios in control tissues were essentially zero.ConclusionsThis rodent model exhibits the key biochemical hallmarks associated with SLOS and displays electrophysiologic deficits comparable to or greater than those observed in the human disease. Clinical Relevance These results predict retinal degeneration in patients with SLOS, particularly those with the more severe (type II) form of the disease, and may be more broadly relevant to other inborn errors of cholesterol biosynthesis. This animal model may also be of use in evaluating therapeutic treatments for SLOS and in understanding the slow phototransduction kinetics observed in patients with SLOS.

Project description:Purpose:Oxidative stress is a common pathological condition for multiple retinal diseases. Hydrogen peroxide (H2O2) has been applied as an oxidative stress inducer for the in vitro studies. Here, we report the in vivo effect of H2O2 exposure to the mouse retina and its underlying mechanism. Methods:The H2O2 or saline solution was intravitreally injected into the eyes of female C57BL/6J mice for two consecutive days. The retinal structure was evaluated by in vivo imaging using spectral domain optical coherence tomography (OCT) and validated by histological assessment as well as retinal marker expression. In addition, retinal stress, cell apoptosis, and antioxidant enzyme expression were also determined. Results:Retinal and outer nuclear layer thickness thinning was observed at days 7 and 14 by OCT imaging with the treatment of 10??g H2O2, which was confirmed by the histopathological analysis. The expressions of photoreceptor (Rho, Rora, Rorb, and Rcvrn), bipolar cell (Chat and Calb2), and retinal pigment epithelial (Rpe65) markers were reduced in the H2O2-treated group, whereas the expression of retinal ganglion cell marker (Tubb3) was increased. TUNEL-positive cells were obviously found in the outer nuclear layer and inner nuclear layer of H2O2-treated mice but sparely found in the ganglion cell layer. Coherently, apoptotic gene expressions (Casp3, Casp9, Bax, and Parp8) were significantly increased in the retina with increasing dosages of H2O2, while Bcl2 expression was mildly decreased. In addition, the expressions of Gfap and antioxidant enzyme genes (Txn2, Sod2, and Gpx4) were significantly upregulated in the retina after the H2O2 treatment, compared to the vehicle control group. Conclusions:This study revealed that intravitreal injection of H2O2 induces acute retinal damage by increasing oxidative stress and cell apoptosis in the retina. This acute retinal degeneration mouse model could provide a platform for drug screening against oxidative stress and retinal diseases.

Project description:BackgroundAge-related macular degeneration (AMD) is one of the major causes of blindness in the elderly over the age of 60. AMD is divided into dry AMD and wet AMD. Although there are certain treatment methods for wet age-related macular degeneration (AMD), there are no effective treatments for dry AMD yet, and finding new drugs or treatment methods for dry AMD has become a priority. For this purpose, this study explored Glabridin (Glab), an isoflavane found in the root extract of licorice, which has never been investigated in relation to eye diseases.PurposeTo investigate the effect of Glab on the sodium iodate (NaIO3) induced retinal degeneration in vitro and in vivo.MethodsIn vitro, cell viability and cytotoxicity were tested with methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay among the groups of ARPE-19 cells. The cell apoptosis was tested with Hoechst 33342 staining and flow cytometry. The level of Reactive oxygen species (ROS) was measured to check the effect on oxidative stress. The protein expressions of phosphorylation of ERK1/2 and p38 were detected by Western blotting. In vivo, C57BL/6J mice were pretreated with Glab intraperitoneally for one week and continued for 4 weeks. NaIO3 was given to mice through tail vein intravenous injection after 1 week of Glab administration. The retinas of mice were monitored by Optical coherence tomography (OCT) and electroretinography (ERG) at 1w, 2w, 3w, and 4w, respectively, followed by H&E staining.ResultsIn vitro, the Glab protected the retinal pigment epithelial (RPE) cells against oxidative stress and apoptosis by inhibiting phosphorylation of ERK1/2 and the p38 MAPK pathway. In vivo, Glab significantly prevented retinal damage by stopping the progression of retinal degeneration and reducing the formation of deposits on the RPE layer induced by NaIO3. According to the findings of electroretinogram (ERG), Glab helped to maintain the normal function of the retina.ConclusionGlabridin has a protective effect against retinal degeneration. It is suggested that Glab be further investigated for the treatment of retinal degeneration diseases.

Project description:We aimed to develop an outer retinal degeneration pig model induced by temporary intravitreal loading of N-methyl-N-nitrosourea (MNU) during vitrectomy. In a preliminary experiment involving 5 mini-pig cases to determine the appropriate concentration of MNU, the vitreous cavity of each eye was filled with 4, 8, 10, 12, or 16 mg/mL MNU for 10 min, which was then replaced with a balanced salt solution. Multimodal examinations including spectral-domain optical coherence tomography (OCT) images and full-field electroretinography (ffERG) were obtained at baseline and week 2, week 6, and week 12. The retinal degeneration was classified according to the amplitudes of a dark adaptive (DA) 10.0 a-wave amplitude. The degree of moderate retinal degeneration was defined as DA 10.0 a-wave amplitude ≥ 10% and < 60% of baseline amplitude. The degree of severe degeneration was defined as DA 10.0 a-wave amplitude < 10% of baseline amplitude, noise, or flat signal. Hematoxylin and eosin staining and immunohistochemistry were performed at week 12. The main experiments were conducted first with 10 cases of 5 mg/mL and later with 13 cases of 10 mg/mL. In the preliminary experiment, degree of outer retinal degeneration increased with MNU concentration. Use of 4, 8, 10, 12, and 16 mg/mL MNU showed no, moderate, severe, severe, and atrophic changes, respectively. In the main experiments, there were 9 cases of moderate retinal degeneration and 1 case of severe degeneration in 5 mg/mL MNU group. Two cases of moderate degeneration and 11 of severe degeneration were recorded in 10 mg/mL group. Mean thickness of total retina, inner nuclear layer, and outer nuclear layer decreased at week 2 in both groups. The mean amplitudes on ffERG decreased at week 2. The ffERG and OCT findings did not change from week 2 to week 6 or week 12. The results of staining supported those of ffERG and OCT. Temporal MNU loading in a vitrectomized pig-eye model induced customized outer retinal degeneration with changing the concentration of MNU.

Dataset Information

Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines.

Publications

Morphologic and electrophysiologic findings of retinal degeneration after intravitreal sodium iodate injection following vitrectomy in canines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets