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A. I. Berta, W. A. Beltran, O. Goldstein, A. Szel, G. M. Acland, G. D. Aguirre; Bimodal Cell Death Kinetics in the STK 38L (erd) Mutant Dog Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4511.
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Early retinal degeneration (erd) is an autosomal recessive, early onset form of canine retinal degeneration characterized by aberrant functional and structural development of rod inner and outer segments, and rod and cone synapses. Abnormal development is followed by rapid degeneration of rods and cones. The erdlocus maps to CFA 27 (homologous to HAS12p), and the disease results from a SINE element insertion in the serine/threonine kinase 38-like protein gene (STK 38L) that causes exon 4 to be skipped during transcription. We now characterize the cell death kinetics and morphological changes in erd mutant retinas.
Paraformaldehyde or Bouin fixed retinas from affected and age-matched controls (ages 4-168 wks), respectively, were embedded in OCT or paraffin. Cell death was assessed with TUNEL labeling, and immunocytochemistry was used to examine expression of photoreceptor-specific and inner retinal markers.
Opsin labeling showed abnormal photoreceptor development characterized by opsin mislocalization, and outer segments of irregular and variable lengths. Expression of cone markers (COS-1, hCAR) was normal until 14 wks of age. Cell death in the ONL is detectable as early as 4.7 wks, and has two peaks, at 7.7 and 11.6 wks; later on, the rate of cell death decreases. In the INL, increased Müller cell expression of vimentin and GFAP, and loss of ON bipolar cells were noted.
Unlike other early onset canine retinal degenerations (rcd1, rcd2, crd1) cell death is delayed in the erd mutant retina until postnatal development of abnormal photoreceptors is completed. Early cell death occurs almost exclusively in rods, and has bimodal kinetics. The bimodal pattern of apoptosis is novel among the previously described retinal degeneration models suggesting that the degeneration mechanism varies among the different mutations.
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