Tyro3 Contributes to Retinal Ganglion Cell Function, Survival and Dendritic Density in the Mouse Retina

Abstract

Retinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic neuritis and ischemic optic neuropathy, resulting in visual defects and blindness. There are currently no therapies in clinical use which can prevent RGC death in optic neuropathies; therefore, the identification of new targets for supporting RGC survival is crucial in the development of novel treatments for eye diseases. In this study we identify that the receptor tyrosine kinase, Tyro3, is critical for normal neuronal function in the adult mouse retina. The loss of Tyro3 results in a reduction in photoreceptor and RGC function as measured using electroretinography. The reduction in RGC function was associated with a thinner retinal nerve fiber layer and fewer RGCs. In the central retina, independent of the loss of RGCs, Tyro3 deficiency resulted in a dramatic reduction in the number of RGC dendrites in the inner plexiform layer. Our results show that Tyro3 has a novel, previously unidentified role in retinal function, RGC survival and RGC morphology. The Tyro3 pathway could therefore provide an alternative, targetable pathway for RGC protective therapeutics.

Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease

“…OCT analysis was undertaken using the Heidelberg Eye Explorer 2 OCT reader plugin (Heyex, Heidelberg Engineering) diameter ring] positioned on the optic nerve head was used for analysis as previously conducted (Blades et al, 2020;Tran et al, 2022).…”

Levodopa Rescues Retinal Function in the Transgenic A53T Alpha-Synuclein Model of Parkinson’s Disease

“…Retinal layer thickness profiles (retinal nerve fibre layer, RNFL; ganglion cell inner plexiform layer, GCIPL; inner nuclear layer, INL; outer plexiform layer, OPL; outer nuclear layer, ONL; total retinal thickness, TRT) were automatically segmented using the Heidelberg Eye Explorer 2 OCT reader plugin (Heyex, Heidelberg Engineering). After the correction of any segmentation errors, an annular grid (Early Treatment Diabetic Retinopathy Study [ETDRS] outer 6 mm diameter ring) was placed on the optic nerve head and mean thickness values from the outer ring quadrants of the grid was used for OCT analysis as previously described [59,62,63].…”

TAM Signaling in the Nervous System

“…Tyro3 promotes survival of hypothalamic Neuropeptide Y + neurons [ 61 ], as well as the survival of retinal ganglion cells (RGC) and the maintenance of RGC dendrites within the inner plexiform layer of the neural retina. This loss of RGCs resulted in a thinner retina, with reduced photoreceptor and RGC function [ 62 ]. While the above examples demonstrate a cell-autonomous protective function for TAM signaling, survival of retinal photoreceptors depends heavily on TAM function in a cell non-autonomous manner.…”