Age-Related Cone Abnormalities in Zebrafish with Genetic Lesions in Sonic Hedgehog
Deborah L. Stenkamp 1*,
Rosanna Satterfield 2,
Kalyani Muhunthan 3,
Tshering Sherpa 3,
Thomas S. Vihtelic 4,
and
David Cameron 5
1 University of Idaho, Department of Biological Sciences, 252 Life Sciences South, Moscow, Idaho, 83844-3051, United States
2 Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States
3 Biological Sciences, University of Idaho, Moscow, Idaho, United States
4 Biological Sciences, University of Notre Dame, Notre Dame, Ohio, United States
5 Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, United States
* To whom correspondence should be addressed. E-mail: dstenkam{at}uidaho.edu.
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Abstract |
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Purpose: Sonic hedgehog (Shh) signaling is required for photoreceptor differentiation and retinal cell survival in embryonic zebrafish. We wished to determine if adult, heterozygous carriers of mutant alleles for the shh gene displayed retinal abnormalities. Methods: Retinal cryosections from young, middle-aged, and senescent wild-type and sonic-you+/- (syu+/-) zebrafish were probed with retinal cell type-specific markers. Contralateral retinal flat-mounts from these fish, and from adult albino zebrafish subjected to light-induced photoreceptor damage followed by regeneration, were hybridized with blue cone opsin cRNA for quantitative analysis of blue cone pattern. Retinal expression of shh mRNA was measured by quantitative RT-PCR. Results: Regions of cone loss and abnormal cone morphology were observed in the oldest syu+/- zebrafish, while no other retinal cell type was affected. This phenotype was age-related and genotype-specific. Cone distribution in the oldest syu+/- zebrafish was predominantly random as assessed by a measure of short-range pattern, while that of wild-type fish and the younger syu+/- zebrafish was statistically regular. A measure of long-range pattern revealed atypical cone aggregation in the oldest syu+/- zebrafish. The light-treated albino zebrafish displayed random cone patterns immediately following light toxicity, but showed cone aggregation upon regeneration. Retinas from the syu+/- fish showed reduced expression of shh mRNA as compared to those of wild-type siblings. Conclusions: The syu+/- zebrafish presents a model for the study of hereditary age-related cone abnormalities. The syu+/- retinas likely experience progressive cone photoreceptor loss, accompanied by cone regeneration. Shh signaling may be required to maintain cone viability throughout life.
Key Words:
cones, regeneration, age-related macular degeneration, light damage, growth factors, genetic diseases
