Tlr2 Gene Deletion Delays Retinal Degeneration in Two Genetically Distinct Mouse Models of Retinitis Pigmentosa

• Published in: International journal of molecular sciences Vol. 22; no. 15; p. 7815
• Main Authors: Sánchez-Cruz, Alonso, Méndez, Andrea C, Lizasoain, Ignacio, de la Villa, Pedro, de la Rosa, Enrique J, Hernández-Sánchez, Catalina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-07-2021; MDPI
• Subjects: Animal models; Animals; Blindness; Cytokines; Degeneration; Disease Models, Animal; Electroretinography; Etiology; Flow cytometry; Gene Deletion; Gene expression; Genetic diversity; IL-1β; Immune response; Inflammation; Innate immunity; Interleukin 1; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; Microglia - cytology; Microglia - metabolism; Microglial cells; Mutation; Neuroprotective Agents; Photoreceptors; Retina; Retinal degeneration; Retinal Degeneration - etiology; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Degeneration - prevention & control; Retinitis; Retinitis pigmentosa; Retinitis Pigmentosa - complications; Therapeutic targets; TLR; TLR2; TLR2 protein; Toll-Like Receptor 2 - physiology; Toll-like receptors; Visual effects; Visual perception; P23H; innate immunity; rd10; retina; neurodegeneration; retinitis pigmentosa; TLR; microglia; TLR2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22157815

Although considered a rare retinal dystrophy, retinitis pigmentosa (RP) is the primary cause of hereditary blindness. Given its diverse genetic etiology (>3000 mutations in >60 genes), there is an urgent need for novel treatments that target common features of the disease. TLR2 is a key activator of innate immune response. To examine its role in RP progression we characterized the expression profile of
and its adaptor molecules and the consequences of
deletion in two genetically distinct models of RP:
(
) and
(
) mice. In both models, expression levels of
and its adaptor molecules increased in parallel with those of the proinflammatory cytokine
. In
mice, deletion of a single
allele had no effect on visual function, as evaluated by electroretinography. However, in both RP models, complete elimination of
attenuated the loss of visual function and mitigated the loss of photoreceptor cell numbers. In
null
mice, we observed decreases in the total number of microglial cells, assessed by flow cytometry, and in the number of microglia infiltrating the photoreceptor layers. Together, these results point to TLR2 as a mutation-independent therapeutic target for RP.