A degenerative retinal process in HIV-associated non-infectious retinopathy.
HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner-retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.
Jacobs Retina Center at the Shiley Eye Center, University of California San Diego, Department of Ophthalmology, La Jolla, California, United States of America.
Igor
I
Kozak
Roman
R
Sasik
William R
WR
Freeman
L James
LJ
Sprague
Maria Laura
ML
Gomez
Lingyun
L
Cheng
Sharif
S
El-Emam
Francesca
F
Mojana
Dirk-Uwe
DU
Bartsch
Jenny
J
Bosten
Radha
R
Ayyagari
Gary
G
Hardiman
D000328:Adult; D002940:Circadian Rhythm; D016000:Cluster Analysis; D003117:Color Vision Defects; D005451:Fluorescein Angiography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D012164:Retinal Diseases / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014158:Transcription, Genetic; D014796:Visual Perception