Loading...
Please wait, while we are loading the content...
A novel RPE65 inhibitor CU239 suppresses visual cycle and prevents retinal degeneration
| Content Provider | Scilit |
|---|---|
| Author | Shin, Younghwa Moiseyev, Gennadiy Petrukhin, Konstantin Cioffi, Christopher L. Muthuraman, Parthasarathy Takahashi, Yusuke Ma, Jian-Xing |
| Copyright Year | 2018 |
| Description | Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease The retinoid visual cycle is an ocular retinoid metabolism specifically dedicated to support vertebrate vision. The visual cycle serves not only to generate light-sensitive visual chromophore 11-cis-retinal, but also to clear toxic byproducts of normal visual cycle (i.e. all-trans-retinal and its condensation products) from the retina, ensuring both the visual function and the retinal health. Unfortunately, various conditions including genetic predisposition, environment and aging may attribute to a functional decline of the all-trans-retinal clearance. To combat all-trans-retinal mediated retinal degeneration, we sought to slow down the retinoid influx from the RPE by inhibiting the visual cycle with a small molecule. The present study describes identification of CU239, a novel non-retinoid inhibitor of RPE65, a key enzyme in the visual cycle. Our data demonstrated that CU239 selectively inhibited isomerase activity of RPE65, with IC50 of 6 μM. Further, our results indicated that CU239 inhibited RPE65 via competition with its substrate all-trans-retinyl ester. Mice with systemic injection of CU239 exhibited delayed chromophore regeneration after light bleach, and conferred a partial protection of the retina against injury from high intensity light. Taken together, CU239 is a potent visual cycle modulator and may have a therapeutic potential for retinal degeneration. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963526/pdf |
| Ending Page | 2429 |
| Page Count | 10 |
| Starting Page | 2420 |
| ISSN | 09254439 |
| e-ISSN | 1879260X |
| DOI | 10.1016/j.bbadis.2018.04.014 |
| Journal | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease |
| Issue Number | 7 |
| Volume Number | 1864 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Biochemistry and Molecular Biology Age-related Macular Degeneration Enzyme Inhibitor Retinal Degeneration Stargardt's Disease Visual Cycle |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Molecular Medicine |
