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Debarshi Mustafi, Krzysztof Palczewski, Hossein Ameri; Features of retinitis pigmentosa defined by high throughput sequencing and wide field imaging. Invest. Ophthalmol. Vis. Sci. 2017;58(8):279.
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© ARVO (1962-2015); The Authors (2016-present)
The pattern of visual field loss in retinal degenerative diseases can be indicative of the primary photoreceptor dysfunction. In primary rod cell diseases, such as in retinitis pigmentosa (RP), symptoms manifest as nyctalopia and peripheral field loss whereas primary cone dystrophies are typified by decreased visual acuity and disruption of color vision. With photoreceptor dysfunction occurring before clinical symptoms, it is imperative to develop approaches to diagnose and understand the potential progression from this subclinical phase.
Genetic analyses were carried out with retinal tissue from primates Macaca fasicularis and Homo sapiens. Tissue from the central and peripheral retinal regions was subjected to library preparation for RNA-sequencing on the Illumina platform. Transcript reads were mapped to their respective genome assemblies and refined manually with RefSeq gene models. Biological replicate tissue allowed for differential expression analysis between central and peripheral retina tissues. Imaging analyses of normal patients and those with clinical features of RP were carried out with swept source optical coherence tomography (SS-OCT). A wide field image acquisition technique was implemented through the mid-peripheral retina.
In the primate retina a total of 11,060 genes were expressed. Of the 207 retinal disease genes expressed, 71 were known RP causing genes with a large proportion preferentially enriched in the peripheral retina. Interrogation of the 807 genes differentially expressed by at least 2-fold between the central and peripheral retina (p<0.05) highlighted the functional relevance of particular pathways involved in maintaining these distinct retinal environments. Single volume acquisitions of SS-OCT from control and RP patients allowed re-construction out to the far periphery for identification and quantification of structural features in the retina and choroid.
High throughput sequencing revealed the underlying biological processes essential to the retina and those disrupted by disease, whereas SS-OCT allowed characterization of structural features unique to normal and diseased retinas. Combinatorial sequencing and imaging approaches outlined here promise to provide novel genotypic-phenotypic insights into common retinal diseases such as RP for future therapeutic strategies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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