Activation of Rod Input in a Model of Retinal Degeneration Reverses Retinal Remodeling and Induces Formation of Functional Synapses and Recovery of Visual Signaling in the Adult Retina

Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)–triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pldnull flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.

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Longitudinal OCT and OCTA monitoring reveals accelerated regression of hyaloid vessels in retinal degeneration 10 (rd10) mice

Scientific Reports ◽

10.1038/s41598-019-53082-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Tae-Hoon Kim ◽

Taeyoon Son ◽

David Le ◽

Xincheng Yao

Keyword(s):

Optical Coherence Tomography ◽

Retinal Degeneration ◽

Vascular System ◽

Retinal Thickness ◽

Wild Type ◽

Physiological Mechanisms ◽

Treatment Protocols ◽

Eye Disorders ◽

Close Relationship ◽

Retinal Remodeling

Abstract The hyaloid vascular system (HVS) is known to have an important role in eye development. However, physiological mechanisms of HVS regression and their correlation with developmental eye disorders remain unclear due to technical limitations of conventional ending point examination with fixed tissues. Here, we report comparative optical coherence tomography (OCT) and OCT angiography (OCTA) monitoring of HVS regression in wild-type and retinal degeneration 10 (rd10) mice. Longitudinal OCTA monitoring revealed accelerated regression of hyaloid vessels correlated with retinal degeneration in rd10. Quantitative OCT measurement disclosed significant distortions of both retinal thickness and the vitreous chamber in rd10 compared to WT mice. These OCT/OCTA observations confirmed the close relationship between HVS physiology and retinal neurovascular development. The distorted HVS regression might result from retinal hyperoxia or dopamine abnormality due to retinal remodeling in rd10 retina. By providing a noninvasive imaging platform for longitudinal monitoring of HVS regression, further OCT/OCTA study may lead to in-depth understanding of the physiological mechanisms of HVS regression in normal and diseased eyes, which is not only important for advanced study of the nature of the visual system but also may provide insights into the development of better treatment protocols of congenital eye disorders.

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Fibroblast Growth Factor (FGF) Soluble Receptor 1 Acts as a Natural Inhibitor of FGF2 Neurotrophic Activity during Retinal Degeneration

Molecular Biology of the Cell ◽

10.1091/mbc.9.10.2785 ◽

1998 ◽

Vol 9 (10) ◽

pp. 2785-2802 ◽

Cited By ~ 32

Author(s):

Xavier Guillonneau ◽

Fabienne Régnier-Ricard ◽

Olivier Laplace ◽

Laurent Jonet ◽

Marijke Bryckaert ◽

...

Keyword(s):

Retinal Degeneration ◽

Glial Cells ◽

Tyrosine Kinase Receptor ◽

Mrna Levels ◽

Fibroblast Growth ◽

Adult Retina ◽

Müller Glial Cells ◽

Neurotrophic Activity ◽

Natural Inhibitor

Fibroblast growth factors (FGF) 1 and 2 and their tyrosine kinase receptor (FGFR) are present throughout the adult retina. FGFs are potential mitogens, but adult retinal cells are maintained in a nonproliferative state unless the retina is damaged. Our work aims to find a modulator of FGF signaling in normal and pathological retina. We identified and sequenced a truncated FGFR1 form from rat retina generated by the use of selective polyadenylation sites. This 70-kDa form of soluble extracellular FGFR1 (SR1) was distributed mainly localized in the inner nuclear layer of the retina, whereas the full-length FGFR1 form was detected in the retinal Muller glial cells. FGF2 and FGFR1 mRNA levels greatly increased in light-induced retinal degeneration. FGFR1 was detected in the radial fibers of activated retinal Muller glial cells. In contrast, SR1 mRNA synthesis followed a biphasic pattern of down- and up-regulation, and anti-SR1 staining was intense in retinal pigmented epithelial cells. The synthesis of SR1 and FGFR1 specifically and independently regulated in normal and degenerating retina suggests that changes in the proportion of various FGFR forms may control the bioavailability of FGFs and thus their potential as neurotrophic factors. This was demonstrated in vivo during retinal degeneration when recombinant SR1 inhibited the neurotrophic activity of exogenous FGF2 and increased damaging effects of light by inhibiting endogenous FGF. This study highlights the significance of the generation of SR1 in normal and pathological conditions.

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