Investigating AMD retinal biomarkers in a rat model of CNV

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Abstract

Purpose:
Retinal biomarkers are of increasing importance in identifying preclinical, clinical and advanced disease progression. In the multifactorial eye disease, age-related macular degeneration (AMD), of which there are two types, wet-AMD is the consequence of choroidal neovascularisation (CNV). The effect of CNV leads to lipid and blood exudation into the retina resulting in tissue damage and the infiltration of inflammatory mediators. The infiltration and proliferation of glial cells, macrophages in addition to secreted cytokines results in excess wound healing, fibrovascular scaring and consequently deterioration of vision. This study will investigate retinal function and pathology associated with CNV formation to identify new retinal biomarkers, and in doing so, could provide vital information in sight preservation.

Methods:
A CNV-laser model was established with female Brown-Norway rats. CNV lesions were induced in one eye of each animal with a 532 nM laser. A longitudinal investigation of 28 days examined retinal function and pathology. Retinal function was investigated with full-field electroretinography (ERG; n=6-12) by analysis of a-wave, b-wave and Oscillatory Potentials (OPs). In vivo imaging was studied by optical coherence tomography (OCT: n=50) and fundus imaging. Hyper-reflective foci (HRF) were further identified and established as retinal biomarkers. Eyes were enucleated and processed for histopathological analysis (n=3-7). A mixed effect model and ANOVA were used for statistical analysis.

Results:
ERG showed reduced retinal function of a-, b-wave and OPs in laser treated eyes. Fundus and OCT examination revealed in vivo retinal biomarkers and HRF. Histological analysis of isolectin-B4, glial activation and infiltration of inflammatory mediators were identified and consistent with changes associated with laser treatment.

Conclusions:
These results suggest that OPs are a more sensitive marker of retinal function and showed progressive decline subsequent to a- and b-wave stabilisation in CNV-laser model. OCT imaging confirmed specific characteristics of CNV changes. However, OCT is limited in its ability to identify the origins of retinal biomarkers. Together with histopathological analysis, retinal biomarker origins could provide vital information for targeted therapeutic intervention in mitigating disease progression.

Layman Abstract:
(optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.
Age-related macular degeneration (AMD) is a multifaceted eye disease affecting over 200 million individuals worldwide. Of the two forms, dry-AMD and wet-AMD, wet-AMD is the most prevalent cause of vision loss worldwide. Despite treatment success, the demanding regime of eye injections and possible complications requires constant review. However, this research looks beyond the current methods of assessment to find new and/or improved tools to determine the hallmarks of disease progression. By capturing information relating to visual function and looking at cells inside the eye in real-time, this study has identified patterns that provide details associated with secondary changes which could highlight important steps along disease progression. This in turn could provide clinicians with an insight into adjusting personalised therapeutic treatment for better outcomes for patients and slight preservation.
Original languageEnglish
Pages1-1
Number of pages1
Publication statusPublished - May 2024
EventAnnual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) 2024 - Seattle, Seattle, United States
Duration: 4 May 20249 May 2024
https://www.arvo.org/meetings/imaging-in-the-eye-conference/

Conference

ConferenceAnnual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) 2024
Abbreviated titleARVO 2024
Country/TerritoryUnited States
CitySeattle
Period4/05/249/05/24
Internet address

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