Exploring the Link Between Retinitis Pigmentosa and Trophic Factor Hypothesis

Published on May 2, 2022

Imagine a dense and vibrant forest where towering trees depend on smaller plants for survival. Similarly, retinitis pigmentosa (RP) is like a magnificent ecosystem within our eyes, where cones, the smaller members, rely on rods, the giants, to thrive. However, this delicate balance is disrupted in RP patients, as their rods begin to dwindle, depriving cones of a vital trophic factor. This trophic factor hypothesis has gained significant support but remains shrouded in mystery. To unravel this enigma, scientists have constructed a mathematical model resembling the spatial dimensions of the retina. By solving an inverse problem using this model, they unearthed experimental conditions that can finally shed light on how the trophic factor mechanism manifests as the captivating patterns of retinal regeneration found in human RP. The research holds promise for developing targeted therapies that could ameliorate vision loss in this prevalent and heartbreaking condition.

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy with a prevalence of about 1 in 4,000, affecting approximately 1.5 million people worldwide. Patients with RP experience progressive visual field loss as the retina degenerates, destroying light-sensitive photoreceptor cells (rods and cones), with rods affected earlier and more severely than cones. Spatio-temporal patterns of retinal degeneration in human RP have been well characterised; however, the mechanism(s) giving rise to these patterns have not been conclusively determined. One such mechanism, which has received a wealth of experimental support, is described by the trophic factor hypothesis. This hypothesis suggests that rods produce a trophic factor necessary for cone survival; the loss of rods depletes this factor, leading to cone degeneration. In this article, we formulate a partial differential equation mathematical model of RP in one spatial dimension, spanning the region between the retinal centre (fovea) and the retinal edge (ora serrata). Using this model we derive and solve an inverse problem, revealing for the first time experimentally testable conditions under which the trophic factor mechanism will qualitatively recapitulate the spatio-temporal patterns of retinal regeneration observed in human RP.

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