Long-term retinal protection by MEK inhibition in Pax6 haploinsufficiency mice

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 Pax6Sey-Neu/+ exhibit a varied degree of ocular damage and impaired vision. Our previous studies showed that these 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, Pax6Sey-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 Pax6Sey-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 Pax6Sey-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.

Original languageEnglish (US)
Article number109012
JournalExperimental eye research
StatePublished - May 2022


  • Aniridia
  • Long-term neuroprotection
  • MEK inhibitor
  • PD0325901
  • Pax6
  • Retinal damage

ASJC Scopus subject areas

  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Ophthalmology


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