Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice
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Pharmacological induction of wild-type PAX6 allele improved ocular abnormalities induced by PAX6 haploinsufficiency in mice.
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In vivo partial rescue of the aniridia phenotype was obtained in an AAK mouse model by either topical or oral administration of the MEK inhibitor PD0325901, which restored normal Pax6 protein levels.
“An in vivo partial rescue of the aniridia phenotype was obtained in an AAK mouse model by either a topical or oral administration treatment with the MEK inhibitor PD0325901, which restored normal Pax6 protein levels [ 172 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [172]
The Methods identify PD0325901 as the drug given orally or topically, and the Results report improved corneal features with both routes in Pax6Sey-Neu/+ mice. The Results show PAX6 protein expression approaching wild-type levels after topical treatment (92 ± 12% versus 100% in wild type), but do not establish that oral treatment also restored PAX6 protein levels. (LLM, conf=0.85)
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“An in vivo partial rescue of the aniridia phenotype was obtained in an AAK mouse model by either a topical or oral administration treatment with the MEK inhibitor PD0325901, which restored normal Pax6 protein levels [172].”
BackgroundDorot, O., Roux, L. N., Zennaro, L., Oved, K., Bremond-Gignac, D., Pichinuk, E., & Aberdam, D. (2022) · The Ocular Surface · doi:10.1016/j.jtos.2021.12.003 · Cited by 18 · see citing works
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Self-citation
- Authors
- Rabiee, B., Anwar, K. N., Shen, X., Putra, I., Liu, M., Jung, R., Afsharkhamseh, N., Rosenblatt, M. I., Fishman, G. A., Liu, X., Ghassemi, M., & Djalilian, A. R.
- Affiliations
- University of Illinois Chicago (US)
- University of Virginia (US)
- Corresponding author
- Djalilian, Ali R.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2020-12-09
- Volume
- 12
- Issue
- 573
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC13102503
- OpenAlex
- W3111351675
- Cited by
- 28
- References
- 69
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 7
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01EY026286, R01EY029121)
- National Eye Institute (R01-EY024349, EY01792)
- Research to Prevent Blindness (Unrestricted Grant, Physician-Scientist Award)
- Eversight
- Vision for Tomorrow
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- Pax6, haploinsufficiency, MEK inhibitors, PD0325901, drug repurposing, corneal opacity, corneal morphology, ocular function, corneal epithelium, mouse model
- MeSH terms
- PAX6 Transcription Factor, Animals, Eye Proteins, Repressor Proteins, Homeodomain Proteins, Gene Dosage, Mice, Paired Box Transcription Factors, Haploinsufficiency
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