Involvement of ER stress in Dry Age-Related Macular Degeneration
Shermin Lak1 , Fatemeh Suri2 , Mozhgan Rezaei Kanavi3 , Hamid Ahmadieh2 , Zahra-Soheila Soheili1 *
- Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract: Age-related macular degeneration (AMD) is a neurodegenerative disease and a leading cause of irreversible blindness in adults over 50 years old. Clinically, AMD is classified into two forms: dry AMD and wet AMD, with approximately 90% of cases being the dry type. The molecular mechanisms underlying dry AMD remain incompletely understood.Endoplasmic Reticulum (ER) stress has been implicated in numerous diseases, including AMD, based on in vitro and animal model studies.
This study is the first to utilize human donor eyes to investigate the expression of ER stress markers and apoptotic pathways in the retinas of dry AMD patients compared to healthy donors.
Methods: Human donor eyes were obtained from the Iranian Eye Bank and classified into three groups: Dry AMD-diagnosed individuals(≥50 years, n=14), Elderly healthy donors (≥50 years, n = 10) as the age-matched controls, and Young healthy donors (≤40 years, n = 10) for assessment of the age-associated changes.
RNA was extracted from the macular region of the retina, and quantitative real-time PCR (qRT-PCR) was conducted to evaluate the expression of GADD153, GRP78, BAX, BCL-2, PTEN, and CASPASE3.
Results: Retinal tissue from AMD patients exhibited significantly elevated expression of ER stress markers (GADD153 and GRP78) and apoptotic genes (BAX and CASPASE3) compared to both young and elderly healthy donors. No significant differences were observed in the expression of PTEN and BCL-2 between the dry AMD group and the healthy controls.
Conclusion: The findings suggest that ER stress is a critical contributor to the development and progression of dry AMD. Targeting ER stress pathways may present a promising therapeutic strategy to prevent retinal cell death and subsequent vision loss in patients with dry AMD.
