Critical Decrease in the Level of Axon Guidance Receptor ROBO1 in Rod Synaptic Terminals Is Followed by Axon...

Area of Science:

• Ophthalmology
• Neuroscience
• Genetics

Background:

• X-linked progressive retinal atrophy 1 (XLPRA1) is a canine disease caused by a RPGR exon ORF15 deletion.
• Photoreceptor degeneration and retinal remodeling are key pathological features of XLPRA1.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms of retinal remodeling in canine XLPRA1.
• To define changes in photoreceptor synaptic terminals and second-order retinal neurons.

Main Methods:

• Analysis of retinas from normal and XLPRA1 mutant dogs.
• Gene expression, Western blot, and immunohistochemistry were employed.
• Cell-specific markers and axon guidance receptors (ROBO1, ROBO2) were examined.

Main Results:

• Rod axon terminals retracted into the outer nuclear layer in mutant retinas, preceding significant rod loss.
• Rod bipolar and horizontal cell processes extended into the outer nuclear layer, forming contacts with rod spherules.
• Markedly decreased ROBO1 levels were observed in rod spherules of predisease and early disease retinas.

Conclusions:

• Depletion of ROBO1 in rod synaptic terminals correlates with retinal remodeling in XLPRA1.
• Reduced ROBO1 may contribute to the retraction of rod axons in XLPRA1.