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Of all of our senses, we rely on vision to provide timely and accurate information so that we can interact with our environment. Visual experience begins when light enters the eye and is focused by the cornea and lens onto the retina. Cone and rod photoreceptors (the primary light sensitive cells in the retina) capture this light and initiate phototransduction, thereby transforming the retinal image to electrical signals that are then relayed from the eye to the brain. The photoreceptors are thus crucial for vision, and diseases that interrupt their function cause blindness. Such diseases include age-related macular degeneration along with most of the more than 220 different types of inherited retinal degenerations. Thus, understanding the structure and function of the photoreceptors and the mechanisms through which they degenerate is critical for developing treatments for blinding conditions.

Dr. Morgan’s laboratory investigates the structure and function of individual photoreceptors in the living human retina, noninvasively. To do this, the lab uses numerous high-resolution retinal imaging techniques, the primary technique being adaptive optics in combination with scanning light ophthalmoscopy (AOSLO). Adaptive optics ophthalmoscopy involves measuring the optical aberrations of a person’s eye and compensating for those aberrations through use of a wavefront corrector such as a deformable mirror. This enables diffraction-limited imaging through the dilated eye, and enables visualization of the cone and rod photoreceptor mosaic noninvasively. 

One goal of the Morgan lab is to use AOSLO to image photoreceptor structure and thereby characterize photoreceptor phenotypes and investigate the mechanisms of photoreceptor degeneration in inherited retinal diseases as compared with normal sighted individuals. For example, Dr. Morgan’s team has shown that patients with Choroideremia can retain normal cone density at many retinal locations while other locations exhibit reduced cone density. However, despite having normal or near normal densities, the Choroideremia patients’ cone photoreceptors showed abnormalities; cones were dim and misshapen and half of patients less than 20 years old displayed hyper-reflective clumps of cones throughout the photoreceptor mosaic. (Morgan et al. “High-Resolution Adaptive Optics Retinal Imaging of Cellular Structure in Choroideremia.” IOVS, 2014;55:6381–6397.) Dr. Morgan’s team continues to study the presentation and progression of photoreceptor degeneration in Choroideremia, and in collaboration with Drs. Aleman, Bennett, and Maguire, is investigating the photoreceptor response to experimental gene therapy. In addition to Choroideremia, Dr. Morgan’s team is investigating photoreceptor involvement in other inherited retinal degenerations including: Stargardt’s, retinitis pigmentosa, and achromatopsia.

A second goal of the Morgan lab is to investigate individual photoreceptor function. Standard tests of visual system function evaluate vision on a significantly coarser scale than that which is routinely used for structural imaging. However, by incorporating functional testing protocols
through the AOSLO imaging system, the lab is able to study photoreceptor function at the same resolution with which they image. The functional protocols in use include: 1) testing sensitivity thresholds of individual cones and small spots using adaptive optics-guided cellular-scale
microperimetry (Tuten et al. "Spatial summation in the human fovea: the effect of optical aberrations and fixational eye movements." JOV, 2018) and 2) measuring stimulus-evoked intrinsic optical signals by quantifying changes in cone near infrared reflectance in response to
visual stimuli (Cooper et al. "Non-invasive assessment of human cone photoreceptor function.” Boomed. Opt. Ex., 2017). One long-term objective of this work is to develop cellular scale functional biomarkers to understand the pathogenesis and progression of retinal disease and assess the safety and efficacy of experimental interventions for these blinding conditions.

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Tuten, WS, Vergilio, GK, Young GJ, Bennett J, Maguire, AM, Aleman, TS, Brainard DH, Morgan JIW: Visual function at the atrophic border in choroideremia assessed with adaptive optics microperimetry. Ophthalmology Retina in press.

Jackson, K, Vergilio GK, Cooper RF, Ying GS, Morgan JIW.: A 2-Year longitudinal study of normal cone photoreceptor density. Investigative Ophthalmology and Visual Science 60(5): 1420-1430, April 2019.

Tuten, WS, Cooper, RF, Tiruveedhula, P, Dubra A, Roorda, A, Cottaris, NP, Brainard, DH, Morgan, JIW. : “Spatial summation in the human fovea: the effect of optical aberrations and fixational eye movements.” Journal of Vision 18(8)(6): 1-18, Aug 2018.

Morgan JIW, Vergilio GK, Hsu J, Dubra A, Cooper RF. : “The reliability of cone density measurements in the presence of rods” Translational Vision Science and Technology 7(3): 21, June 2018.

Bryant L, Lozynska O, Han G, Morgan JIW, Gai X, Maguire AM, Aleman T, Bennett J. : On variants and disease-causing mutations: Case studies of a SEMA4A variant identified in inherited blindness. Ophthalmic Genetics 39(1): 144-146, Jan 2018.

Cooper RF, Tuten WS, Dubra A, Brainard DH, Morgan JIW: “Non-invasive assessment of human cone photoreceptor function.” Biomedical Optics Express 27(8): 5098-5112, Nov 2017.

Hwang CK, Kolomeyer AM, Brucker AJ, Morgan JIW, Nichols CW, Aleman TS. : “Localized bilateral juxtafoveal photoreceptor loss in POEMS: A new association.” Retina. 37(7): e91-92, July 2017.

Aleman TA, Han G, Serrano LW, Fuerst NM, Charlson ES, Pearson DJ, Chung DC, Traband A, Pan W, Ying G, Bennett J, Maguire AM, Morgan JIW. : Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study.” Ophthalmology 124(3): 359-373, Mar 2017.

Chen M, Cooper RF, Han GK, Gee J, Brainard DH, Morgan JIW.: Multi-modal automatic montaging of adaptive optics retinal images. Biomedical Optics Express 7(12): 4899-4918, Nov 2016.

Morgan, JIW: The fundus photo has met its match: OCT and AO are here to stay. Ophthalmic and Physiological Optics 36(3): 218-39, May 2016.

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