StriatechJournal Club

Inherited Retinal Dystrophy: Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration

T.J. Hollingsworth, PhD - University of Tennessee Health Science Center
C57B/6J mouse retinal section immunolabeled for the photoreceptor protein rhodopsin in magenta and rootletin, a protein comprising the ciliary rootlet of the photoreceptor outer segment connecting cilium. Nuclei labeled with DAPI in blue. These cells are one of the two photoreceptor cell types affected by inherited retinal dystrophies.

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The BXD32 mouse is a model of polygenic inheritance retinal dystrophy (IRD). IRD is a set of congenital heterogenous blinding diseases caused by the death of rod and cone photoreceptors of the retina. Patients with IRDs can begin losing sight as early as childhood and can be completely blind by adolescence. They may also begin losing sight as an adult and blind in older age. The age of onset and rate of degeneration varies with the gene that is mutated and other genetic and environmental factors. A commonality amongst these diseases is the presence of overactive inflammatory cells and pathways. In this study, using various methods including optomotor behavioral measurements with Striatech’s OptoDrum, electroretinography, optical coherence tomography, funduscopy, and immunohistochemistry, we have shown that this chronically elevated proinflammatory environment is not only a byproduct of the degenerative disease, but an actual driver of the disease itself.

Key Topics

  • IRD signs, symptoms, and endophenotypes
  • The genes that underly the IRD diseases
  • Current treatments and possible future treatments and cures

Learning Objectives

Scienctists should be able to understand the hallmarks of IRDs including signs and symptoms of IRDs as well as the endophenotypes of IRDs. They should also learn  the genetic factors underlying IRDs and how these interplay with the retina and other organ systems. They will also learn about possible treatments for IRDs and where the scientific and medical communities are in the treatment of and cures for IRDs.

Background Reading

Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration in a Spontaneous Polygenic Model of Inherited Retinal Dystrophy. Hollingsworth TJ, Wang X, White WA, Simpson RN, Jablonski MM.
Front Pharmacol. 2022 Mar 21;13:839424.
doi: 10.3389/fphar.2022.839424.

The Severe Autosomal Dominant Retinitis Pigmentosa Rhodopsin Mutant Ter349Glu Mislocalizes and Induces Rapid Rod Cell Death. Hollingsworth, T. J., and Gross, A. K. (2013).
J. Biol. Chem. 288 (40), 29047–29055.
doi: 10.1074/jbc.M113.495184

Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa. Hollingsworth, T. J., Hubbard, M. G., Levi, H. J., White, W., Wang, X., Simpson, R., et al. (2021).
Biomolecules 11 (8), 1163.
doi: 10.3390/biom11081163

Using BXD Mouse Strains in Vision Research: A Systems Genetics Approach. Geisert, E. E., and Williams, R. W. (2020).
Mol. Vis. 26, 173–187.
PMID: 32180682

A Platform for Experimental Precision Medicine: The Extended BXD Mouse Family. Ashbrook, D. G., Arends, D., Prins, P., Mulligan, M. K., Roy, S., Williams, E. G., et al. (2021).
Cell Syst 12 (3), 235.
doi: 10.1016/j.cels.2020.12.002


Defective Trafficking of Rhodopsin and its Role in Retinal Degenerations. Hollingsworth, T. J., and Gross, A. K. (2012).
Int. Rev. Cel Mol Biol 293, 1–44.
doi: 10.1016/B978-0-12-394304-0.00006-3

Inflammation in the Pathogenesis of Progressive Retinal Dystrophies. Jordan, K. E., Jablonski, M. M., and Hollingsworth, T. J. (2021).
J. Ophthalmic Res. Vis. Care 1 (1).
doi: 10.54289/JORVC2100103

About the speaker

T.J. Hollingsworth, PhD

T.J. Hollingsworth, PhD

Assistant Professor
University of Tennessee Health Science Center


T.J. received his PhD from the Vision Science Graduate Program at the University of Alabama at Birmingham in 2013 and completed two postdocs at the University of Oklahoma Health Science Center and at the University of Tennessee Health Science Center (UTHSC) by 2015. From 2015 to 2019, T.J. was the technical director of the Neuroscience Institute Imaging Facility and became a faculty member in the Department of Ophthalmology at UTHSC in 2019. Since then, T.J. has been working with his faculty mentor, Dr Monica M. Jablonski, to study age-related macular degeneration, glaucoma and inherited retinal dystrophies.

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