Abstract
Purpose :
PROM1, a pentaspan transmembrane glycoprotein in photoreceptor discs, is linked to various retinal diseases. We aimed to investigate if dark rearing protects vision in PROM1-deficient animals, seeking new treatments for these conditions.
Methods :
In this study, we utilized two mouse models, rd19 and prom1-creERT2 (prom1-/-), from Jackson Labs to study the role of PROM1 in the retina. We also accounted for the known variation in RPE65 by studying Rd19 in Leucine or Methione at position 450. We measured photoreceptor response via electroretinography (ERG) throughout their post-natal (P) development (P12-P250). We also examined the impact of dark rearing on PROM1-mediated degeneration. A range of techniques, including Proteomics, Immunohistochemistry, Morphological Assessments, and TEM imaging, were employed, with wild-type littermates serving as controls.
Results :
Our study found that PROM1 is essential for vision and photoreceptor development. We observed a significant reduction in photoreceptor response from P12 -P250 (p value=2.37x10^-8) in the absence of PROM1. At P12, PROM1-deficient animals showed a two-fold reduction (p-value=9.28x10^-4) in scotopic photoreceptor response compared to their wild-type littermates. Despite no initial photoreceptor degeneration, there was an increased glial cell activation, a sign of cell damage. Contrary to our expectations, dark rearing did not mitigate photoreceptor degeneration or vision loss in any model tested. Ultrastructural analysis revealed malformed outer segments characterized by whorl-like continuous membrane. Additionally, there is a significant reduction in rod photoreceptor outer segment proteins, including Rhodopsin.
Conclusions :
PROM1 is essential for proper photoreceptor development and visual acuity. Impaired photoreceptor response in PROM1-deficient animals was evident from P12 before eye-opening. In the animal models tested, dark rearing does not reverse the vision impairment due to the absence of PROM1. The lack of PROM1 leads to abnormal outer segment disc morphology and reduced expression of key phototransduction proteins. Our results underscore the vital role of PROM1 in maintaining healthy vision and normal photoreceptor development.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.