Cone structure in retinal degeneration associated with mutations in the peripherin/RDS gene.
OBJECTIVE
To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS.


METHODS
High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient.


RESULTS
Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient.


CONCLUSIONS
peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure.
Department of Ophthalmology, UCSF School of Medicine, 10 Koret Way, Room K-129, San Francisco, CA 94143-0730, USA. duncanj@vision.ucsf.edu
Jacque L
JL
Duncan
Katherine E
KE
Talcott
Kavitha
K
Ratnam
Sanna M
SM
Sundquist
Anya S
AS
Lucero
Shelley
S
Day
Yuhua
Y
Zhang
Austin
A
Roorda
D000328:Adult; D000368:Aged; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009887:Ophthalmoscopy; D064531:Peripherins; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D055815:Young Adult
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins