Characterization of Outer Retinal Morphology with High-Speed, Ultrahigh-Resolution Optical Coherence Tomography

Srinivasan, Vivek J.; Monson, Bryan K.; Wojtkowski, Maciej; Bilonick, Richard A.; Gorczyńska, Iwona; Chen, Royce; Duker, Jay S.; Schuman, Joel S.; Fujimoto, James G.

doi:10.1167/iovs.07-0838

Cited by 258 publications

(211 citation statements)

References 40 publications

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“…Peaks and transitions between hypo-and hyper-reflective laminae were segmented directly using individual LRPs by the minima and maxima of the signal and its slope. For the outer retinal sublaminae, signal peak assignments were based on previously published work (30).…”

Section: Methodsmentioning

confidence: 99%

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations

Sakami

Maeda

Bereta³

et al. 2011

Journal of Biological Chemistry

234

362

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Rhodopsin, the visual pigment mediating vision under dim light, is composed of the apoprotein opsin and the chromophore ligand 11-cis-retinal. A P23H mutation in the opsin gene is one of the most prevalent causes of the human blinding disease, autosomal dominant retinitis pigmentosa. Although P23H cultured cell and transgenic animal models have been developed, there remains controversy over whether they fully mimic the human phenotype; and the exact mechanism by which this mutation leads to photoreceptor cell degeneration remains unknown. By generating P23H opsin knock-in mice, we found that the P23H protein was inadequately glycosylated with levels 1-10% that of wild type opsin. Moreover, the P23H protein failed to accumulate in rod photoreceptor cell endoplasmic reticulum but instead disrupted rod photoreceptor disks. Genetically engineered P23H mice lacking the chromophore showed accelerated photoreceptor cell degeneration. These results indicate that most synthesized P23H protein is degraded, and its retinal cytotoxicity is enhanced by lack of the 11-cisretinal chromophore during rod outer segment development.Greater understanding of a genetically heterogeneous group of retinal disorders is now possible due to the results of studies that have revealed their causative genes. Many genetic loci can cause such retinopathies (RetNet) (1). Mutations in phototransduction genes, including those in opsin genes (2), constitute one of the major known causes of inherited blinding diseases (3). Among them, retinitis pigmentosa (RP) 2 refers to a group that displays genetic heterogeneity and a range of clinical phenotypes (4). RP manifested predominantly by death of rod photoreceptor cells is a progressive disease characterized by night blindness that progresses to loss of peripheral vision and eventually all useful vision over decades (5). Of more than 100 mutant opsins associated with autosomal dominant RP (adRP), the most frequent mutation is P23H (6), accounting for ϳ10% of human cases (7,8).In vitro studies have shown that the P23H opsin associated with adRP is misfolded and retained in the ER (9 -12). Consequently, this protein is not transported to the cell membrane (12) but instead was degraded by the ubiquitin-proteosome system (13). Co-expression of adRP-linked opsin folding-deficient mutants and wild type (WT) opsin resulted in enhanced proteosome-mediated degradation and steady-state ubiquitination of both mutant and WT opsin in an experimental cell line (14). These results imply that in vivo, a misfolded monomer of P23H opsin can also induce co-aggregation with WT rhodopsin preventing rod outer segment (ROS) formation. This dominant negative effect on ROS formation has been considered as the underlying reason for the adRP inheritance of P23H in humans.The retinal structure in heterozygous transgenic mice and rats expressing the P23H opsin partially mimics that of adRP in humans carrying this mutation (15)(16)(17)(18)(19). Mislocalization of the P23H opsin in the retina also has been reported in transgenic ani...

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Section: Methodsmentioning

confidence: 99%

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations

Sakami

Maeda

Bereta³

et al. 2011

Journal of Biological Chemistry

234

362

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“…The OS/RPE junction line is also named cone outer segment tip (COST) line and represents a thin line between the IS/OS junction and RPE [19]. However, lately Spaide and Curcio have raised a debate regarding the anatomical assignments of these four lines.…”

Section: Spectral-domain Optical Coherence Tomographymentioning

confidence: 99%

Optical coherence tomography imaging in uveitis

et al. 2013

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“…Spectral domain OCT (SD OCT) technology has led to progress in outer retinal layer segmentation to enable specific layer measurements, such as photoreceptor length and outer segment length, although the algorithms have been thus far applied to eyes with no known disease or a few selected pathologies. [15][16][17][18][19][20] Controversy still exists in the identification of precise outer retinal layers. 18,21 The disruption of retinal architecture in pathology poses a challenge to the segmentation algorithm, which could result in erroneous thickness measurements.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19][20] Controversy still exists in the identification of precise outer retinal layers. 18,21 The disruption of retinal architecture in pathology poses a challenge to the segmentation algorithm, which could result in erroneous thickness measurements. 22 Integrity of the photoreceptor inner segment-outer segment (IS-OS) junction has been shown to correlate well with VA in cross sectional studies of patients with diabetic macular oedema, RVOs, and neovascular age-related macular degeneration.…”

Section: Introductionmentioning

confidence: 99%

Association of outer retinal layer morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13

Domalpally

Peng

Danis

et al. 2012

Eye

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Purpose To assess associations between visual acuity (VA) and the status of the photoreceptor inner segment-outer segment (IS-OS) junction in a subset of patients in the Standard Care vs COrticosteroid for REtinal Vein Occlusion (SCORE) Study. Methodology High-resolution time domain optical coherence tomography (OCT) scans of study eyes from a single site participating in the SCORE Study were evaluated. Integrity of the IS-OS junction in the central subfield was evaluated using a three-step scale: absent, abnormal or normal. Associations of the IS-OS status with ETDRS VA letter score and center point thickness (CPT) were investigated. Results Baseline OCTs of 42 eyes were evaluated. The IS-OS junction was absent in 30 (71%) and abnormal in 12 (29%). At month 12, the IS-OS junction was absent in 18 (43%), abnormal in 12 (28%), and normal in 12 (28%) eyes. At baseline, IS-OS status was significantly associated with CPT, but not with VA. At month 12, IS-OS status was significantly associated with CPT and VA, that is, absent or abnormal IS-OS was associated with increased CPT and worse VA. Change in IS-OS status was not associated with change in CPT (P ¼ 0.8). Worsening of IS-OS status was associated with loss of VA and improvement in IS-OS status to normal was associated with gain in VA (P ¼ 0.03). Conclusion In this data set with long-term follow-up of OCTs as part of the SCORE Study, there is a correlation between change in IS-OS status and VA. This supports further evaluation of outer retinal morphology in larger data sets.

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Characterization of Outer Retinal Morphology with High-Speed, Ultrahigh-Resolution Optical Coherence Tomography

Cited by 258 publications

References 40 publications

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations

Probing Mechanisms of Photoreceptor Degeneration in a New Mouse Model of the Common Form of Autosomal Dominant Retinitis Pigmentosa due to P23H Opsin Mutations

Optical coherence tomography imaging in uveitis

Association of outer retinal layer morphology with visual acuity in patients with retinal vein occlusion: SCORE Study Report 13

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