Posted on

Suppressing Thyroid Hormone Signaling Preserves Cone Photoreceptors in Mouse Models of Retinal Degeneration

Slide 1

This abstract was presented today at the 2014 Association for Research in Vision and Opthalmology (ARVO) meetings in Orlando, Florida by Xi-Qin Ding, Hongwei Ma, Arjun Thapa, Lynsie Morris, T M. Redmond and Wolfgang Baehr.

Full size poster available here.

Purpose: Cone phototransduction and survival of cones in the human macula is essential for color vision and for visual acuity. Progressive cone degeneration in age-related macular degeneration, Stargardt disease, and recessive cone dystrophies is a major cause of blindness. Thyroid hormone (TH) signaling which regulates cell proliferation, differentiation, and apoptosis plays a central role in cone opsin expression and patterning in the retina. Here, we investigated whether TH signaling affects cone viability in inherited retinal degeneration mouse models.

Methods: Rpe65-/- mice (a model of severe Leber congenital amaurosis or LCA) and Cpfl1mice (severe recessive achromatopsia) were used to determine whether suppressing TH signaling (with anti-thyroid treatment) reduces cone death. Further, Cngb3-/- mice (moderate achromatopsia) and Gucy2e-/- mice (moderate LCA) were used to determine whether stimulating TH signaling (with triiodothyronine (T3) treatment) deteriorates cones. The serum T3 levels were analyzed by ELISA. Cone and rod survival were evaluated by examining cone density and expression levels of cone specific proteins using immunohistochemical and biochemical approaches, and by examining morphological integrity of the retinas.

Results: Cone density increased about 6-fold in Rpe65-/- and cpfl1 mice following anti-thyroid treatment and decreased about 40% inCngb3-/- and Gucy2e-/- mice following T3 treatment. Anti-thyroid treatment did not affect rod survival, manifested as unchanged outer nuclear layer (ONL) thickness and the number of nuclei in ONL. However, T3 treatment significantly reduced ONL thickness and the number of nuclei in ONL in Cngb3-/- andGucy2e-/- mice.
Conclusions: With multiple retinal degeneration mouse models, we demonstrate that TH signaling regulates photoreceptor viability in degenerating retinas. Suppressing TH signaling protects cones whereas stimulating TH signaling has a negative effect on both cones and rods. The findings of this study provide new insights into cone preservation and therapeutic interventions.

Posted on

New Webvision Chapter: Evolution of Phototransduction, Vertebrate Photoreceptors and Retina

Branchiostoma_lanceolatum

After much work by a number of our contributors, not the least of whom is the author of this particular effort, we have a spectacular new addition to Webvision:  A section on the Evolution of Phototransduction, Vertebrate Photoreceptors and Retina by Trevor D. Lamb.  Be sure to check it out and let us know what you think in the comments.

Continue reading “New Webvision Chapter: Evolution of Phototransduction, Vertebrate Photoreceptors and Retina”

Posted on

Notable Paper: The Molecular Mechanism of Thermal Noise in Rod Photoreceptors

 

Phototransduction is the process by which photon capture by opsins in photoreceptors is transduced into a neural signal.    However, there are limits on visual sensitivity that are imposed by thermal means as opposed to the photochemical mechanisms resulting in activation of the phototransduction cascade.

The mechanism of this limit has long been a matter of debate, however this paper by Samer Gozem, Igor Schapiro, Nicolas Ferré and Massimo Olivucci demonstrates a mechanism.  Mechanistically, the authors examined the maximum absorption wavelength (λmax) and the thermal activation kinetic constant (k) of different visual pigments which indicates that the thermal and photochemical activations are related.  The authors found that rod opsin or rhodopsin possesses a transition state for thermal activation that has the same electronic structure as it does for photo-excitation.  This results in spontaneous and random signals being generated in the rod photoreceptors that impose limits on visual sensitivity.   Continue reading “Notable Paper: The Molecular Mechanism of Thermal Noise in Rod Photoreceptors”