Abstract
Purpose :
Our hypothesis posits that targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) within the Akt pathway holds the potential for treating retinitis pigmentosa (RP). This comprehensive review analyzes murine models using Bisperoxovanadium (bpV) and Rasagiline to investigate the shared apoptotic pathway in rod photoreceptors implicated in RP and retinal detachment (RD).
Methods :
This literature review utilized keywords to retrieve articles from PubMed. Articles in English between 2000 and 2023 were considered, resulting in the initial selection of 28 articles. Following exclusion criteria related to date range and thematic focus, 14 studies were included. This review covers biochemical pathways and drugs targeting enzymes in murine models. Excessive dosage implications are uncertain due to the lack of established medication dosages.
Results :
Research investigations involving Rasagiline, a pharmaceutical agent recognized for inducing the overexpression of the Bcl-2 protein, a downstream factor in the PI3K-Akt signaling pathway reveal that mice with the rd10 genotype for RP, demonstrated significant improvements in both visual acuity and the electrical responses of photoreceptors to light stimuli after 30 days of treatment. Furthermore, the drug demonstrated efficacy in attenuating photoreceptor degeneration, with a decrease in the pro-apoptotic factor Bax and an increase in the antiapoptotic factor Bcl-2.
In another experimental investigation, Mao et al. focused on using bpV, a PTEN inhibitor in the PI3K/Akt pathway for RD. It was determined that animals treated with the drug displayed diminished photoreceptor apoptosis and preserved retinal thickness post-retinal detachment compared to the control group. Additionally, the treatment resulted in increased levels of p-Akt, PDK-1, p-BAD, and Bcl-2, and decreased levels of cytochrome c and cleaved caspase-3 (Figure 1).
Conclusions :
The inhibition of PTEN leads to elevated levels of p-Akt enzyme, facilitates Bcl-2 overexpression, and diminishes pro-apoptotic factors such as cytochrome c and cleaved caspase-3 after RD. The recognition of shared molecular pathways leading to photoreceptor death implicated in both RP and RD establishes a unifying rationale for our proposed treatment approach of targeting PTEN to protect rod photoreceptors in both diseases.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.