Ultrastructural Analysis of Zebra Fish (Daniorerio) DHDDS Retinitis Pigmentosa Disease Model Functionally Links DHDDS to Mitochondrial and Membrane Dysfunction
Jeffrey S. Prince, Julia Dallman, Scott Miyazaki, Rong Wen

Abstract
A mutation in the enzyme dehydrodolichyldiphosphate synthase (DHDDS) has been causally linked to human retinitis pigmentosa (RP), a disease associated with late onset blindness due to loss of photoreceptors in the eye. Indeed, knock-down models of DHDDS in zebrafish are blind with reduced or absent photoreceptor outer segments, confirming the causal relationship between DHDDS and vision. To address mechanisms by which DHDDS knock-down disrupts photoreceptor outer segments, we used electron microscopy to examine the ultra structure of the retina at two developmental stages, one before (31 hours post-fertilization, hpf) and the other after (104 hpf) outer segments and associated vision normally develop. We identify at least three different ultra structural traits that distinguished mitochonrdria in DHDDS knock-down and control fish at both time points suggesting that early mitochondrial dysfunction may underlie the later deficits in the development of photoreceptor outer segments. In addition, other membrane systems (those surrounding guanine crystals in the iridophore layer and melanin pigment granules in the pigmented epithelial layer) were compromised.

Full Text: PDF     DOI: 10.15640/aijb.v4n2a3