Long-term retinal protection by MEK inhibition in Pax6 haploinsufficiency mice
| Autor: | James D. Cole, Kara M. McHaney, Behnam Rabiee, Jingyi Gao, Carlos Rodriguez, David A. Miller, Mingna Liu, Marta Grannonico, Pedro Norat, Hao F. Zhang, Ali R. Djalilian, Xiaorong Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Homeodomain Proteins
Mitogen-Activated Protein Kinase Kinases PAX6 Transcription Factor Haploinsufficiency Sensory Systems Article Retina Repressor Proteins Cellular and Molecular Neuroscience Ophthalmology Disease Models Animal Mice Animals Humans Paired Box Transcription Factors Eye Proteins Aniridia |
| Zdroj: | Exp Eye Res |
| Popis: | Aniridia is a panocular condition characterized by impaired eye development and vision, which is mainly due to the haploinsufficiency of the paired-box-6 (PAX6) gene. Like what is seen in aniridia patients, Pax6-deficient mice Pax6(Sey-Neu/+) exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that theses phenotypes were partially rescued by PD0325901, a mitogen-activated protein kinase kinase (MEK or MAP2K) inhibitor. In this study, we assessed the long-term efficacy of PD0325901 treatment in retinal health and visual behavior. At about one year after the postnatal treatment with PD0325901, Pax6(Sey-Neu/+) mice showed robust improvements in retina size and visual acuity, and the elevated intraocular pressure (IOP) was also alleviated, compared to age-matched mice treated with vehicles only. Moreover, the Pax6(Sey-Neu/+) eyes showed disorganized retinal ganglion cell (RGC) axon bundles and retinal layers, which we termed as hotspots. We found that the PD treatment reduced the number and size of hotspots in the Pax6(Sey-Neu/+) retinas. Taken together, our results suggest that PD0325901 may serve as an efficacious intervention in protecting retina and visual function in aniridia-afflicted subjects. |
| Databáze: | OpenAIRE |
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