Ubiquitous Chromatin Modifiers in Congenital Retinal Diseases: Implications for Disease Modeling and Regenerative Medicine

Brian W Basinski; Daniel A Balikov; Michael Aksu; Qiang Li; Rajesh C Rao

doi:10.1016/j.molmed.2021.01.001

Ubiquitous Chromatin Modifiers in Congenital Retinal Diseases: Implications for Disease Modeling and Regenerative Medicine

Trends Mol Med. 2021 Apr;27(4):365-378. doi: 10.1016/j.molmed.2021.01.001. Epub 2021 Feb 8.

Authors

Brian W Basinski¹, Daniel A Balikov², Michael Aksu², Qiang Li², Rajesh C Rao³

Affiliations

¹ Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
² Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA.
³ Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI, USA; Section of Ophthalmology, Surgery Service, Veterans Administration Ann Arbor Healthsystem, Ann Arbor, MI, USA. Electronic address: rajeshr@umich.edu.

Abstract

Retinal congenital malformations known as microphthalmia, anophthalmia, and coloboma (MAC) are associated with alterations in genes encoding epigenetic proteins that modify chromatin. We review newly discovered functions of such chromatin modifiers in retinal development and discuss the role of epigenetics in MAC in humans and animal models. Further, we highlight how advances in epigenomic technologies provide foundational and regenerative medicine-related insights into blinding disorders. Combining knowledge of epigenetics and pluripotent stem cells (PSCs) is a promising avenue because epigenetic factors cooperate with eye field transcription factors (EFTFs) to direct PSC fate - a foundation for congenital retinal disease modeling and cell therapy.

Keywords: blindness; development; epigenetics; retina; stem cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Anophthalmos / genetics
Anophthalmos / therapy
Blindness / etiology
Blindness / genetics
Blindness / therapy
Cell- and Tissue-Based Therapy* / methods
Cell- and Tissue-Based Therapy* / trends
Chromatin / pathology*
Coloboma / genetics
Coloboma / therapy
Congenital Abnormalities / genetics
Congenital Abnormalities / therapy
Disease Models, Animal
Epigenomics
Humans
Microphthalmos / genetics
Microphthalmos / therapy
Pluripotent Stem Cells
Regenerative Medicine / methods
Regenerative Medicine / trends
Retina / cytology
Retina / pathology
Retinal Diseases / genetics*
Retinal Diseases / therapy
Transcription Factors* / genetics
Transcription Factors* / metabolism

Substances

Chromatin
Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding