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Updated: Apr 26, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
[Expression of nitric oxide synthases in the retina of OXYS rats during retinopathy development]
Abstract:
Both the lack and excess generation of nitric oxide (NO) contributes to the pathogenesis of age-related diseases, according to the latest data including age-related macular degeneration (AMD), which is a leading cause of vision loss in people over 65. The mechanisms of the effects of NO are not entirely clear, the information about changes in the expression synthase NO (NOSs) in the retina with age and the development of AMD are limited. We showed previously that the senescence-accelerated OXYS rats strain is an animal model of AMD. The purpose of the present research was to compare the transcriptional activity of genes NOSs: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS) in the retina OXYS and Wistar rats (used as control) by real-time PCR. The study was carried out on animals at the age of 3 and 18 months during the period of manifestation and active progression of AMD-like retinopathy in OXYS rats. We showed that mRNA level of NOSs was not dependent on age in Wistar and OXYS rats. Interstrain differences in the level of eNOS mRNA were not detected, but the level of mRNA of nNOS in the retina of 18-month-old OXYS rats was 2,4 times higher than in age-matched Wistar rats. Regardless of age the level of iNOS mRNA in OXYS rats was 7 times lower than that in Wistar rats, but the protein content of iNOS in 3-month-old OXYS rats (ELISA data) was increased. Perhaps such a paradoxical situation reflects a decreased reactivity of the immune system in the OXYS rats.
Insights
Nitric oxide synthase (NOS) gene expression in the retina differs between OXYS rats, an animal model for age-related macular degeneration (AMD), and Wistar rats. Specifically, nNOS mRNA was higher, and iNOS mRNA was lower in OXYS rats.
Area of Science:
- Ophthalmology and Vision Science
- Molecular Biology
- Aging Research
Context:
- Nitric oxide (NO) plays a complex role in age-related diseases, including age-related macular degeneration (AMD).
- The precise mechanisms of NO's involvement and changes in nitric oxide synthase (NOS) gene expression in the aging retina, particularly in AMD, remain unclear.
- The OXYS rat strain has been identified as a relevant animal model for studying AMD.
Purpose:
- To compare the transcriptional activity of neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS) genes in the retinas of OXYS rats and control Wistar rats.
- To investigate these differences at 3 and 18 months of age, corresponding to the progression of AMD-like retinopathy in OXYS rats.
Summary:
- Real-time PCR analysis revealed no age-dependent changes in NOS mRNA levels in either rat strain.
- While eNOS mRNA levels were similar between strains, 18-month-old OXYS rats showed a 2.4-fold increase in retinal nNOS mRNA compared to Wistar rats.
- Conversely, iNOS mRNA levels were 7-fold lower in OXYS rats across all ages, despite increased iNOS protein content at 3 months, suggesting potential immune system dysregulation.
Impact:
- This study elucidates specific alterations in NOS gene expression associated with AMD pathogenesis in the OXYS rat model.
- Findings highlight a potential link between altered nNOS and iNOS expression/activity and the development of retinopathy.
- The paradoxical iNOS findings suggest complex immune system interactions in the aging retina, warranting further investigation.
