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Article

Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa

1
Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
2
Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Hemant Khanna and Massimo Dal Monte
Biomolecules 2021, 11(8), 1163; https://doi.org/10.3390/biom11081163
Received: 10 May 2021 / Revised: 17 July 2021 / Accepted: 3 August 2021 / Published: 6 August 2021
(This article belongs to the Special Issue Ocular Diseases and Therapeutics)
Retinitis pigmentosa (RP) is a hereditary disease of the retina that results in complete blindness. Currently, there are very few treatments for the disease and those that exist work only for the recessively inherited forms. To better understand the pathogenesis of RP, multiple mouse models have been generated bearing mutations found in human patients including the human Q344X rhodopsin knock-in mouse. In recent years, the immune system was shown to play an increasingly important role in RP degeneration. By way of electroretinography, optical coherence tomography, funduscopy, fluorescein angiography, and fluorescent immunohistochemistry, we show degenerative and vascular phenotypes, microglial activation, photoreceptor phagocytosis, and upregulation of proinflammatory pathway proteins in the retinas of the human Q344X rhodopsin knock-in mouse. We also show that an FDA-approved pharmacological agent indicated for the treatment of rheumatoid arthritis is able to halt activation of pro-inflammatory signaling in cultured retinal cells, setting the stage for pre-clinical trials using these mice to inhibit proinflammatory signaling in an attempt to preserve vision. We conclude from this work that pro- and autoinflammatory upregulation likely act to enhance the progression of the degenerative phenotype of rhodopsin Q344X-mediated RP and that inhibition of these pathways may lead to longer-lasting vision in not only the Q344X rhodopsin knock-in mice, but humans as well. View Full-Text
Keywords: retinal degeneration; retinitis pigmentosa; rhodopsin; inflammation; microglia; TNFα, NF-κB; JAK/STAT; NLRP3 retinal degeneration; retinitis pigmentosa; rhodopsin; inflammation; microglia; TNFα, NF-κB; JAK/STAT; NLRP3
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MDPI and ACS Style

Hollingsworth, T.J.; Hubbard, M.G.; Levi, H.J.; White, W.; Wang, X.; Simpson, R.; Jablonski, M.M.; Gross, A.K. Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa. Biomolecules 2021, 11, 1163. https://doi.org/10.3390/biom11081163

AMA Style

Hollingsworth TJ, Hubbard MG, Levi HJ, White W, Wang X, Simpson R, Jablonski MM, Gross AK. Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa. Biomolecules. 2021; 11(8):1163. https://doi.org/10.3390/biom11081163

Chicago/Turabian Style

Hollingsworth, T.J., Meredith G. Hubbard, Hailey J. Levi, William White, Xiangdi Wang, Raven Simpson, Monica M. Jablonski, and Alecia K. Gross. 2021. "Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa" Biomolecules 11, no. 8: 1163. https://doi.org/10.3390/biom11081163

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