Wednesday, May 15, 2024
5/15/2024
PROJECT SUMMARY Melanin is naturally present in the eye within the choroid, iris, and retinal pigment epithelium (RPE), a single layer of epithelial cells located posterior to the photoreceptors in the retina. Changes in retinal pigmentation normally happen with aging and are present in many ocular diseases. For example, age-related macular degeneration (AMD) is the predominant cause of vision loss in adults over 65 years old in the US and involves dysfunction of the RPE and changes in pigmentation. In early stages, AMD is usually characterized by changes in pigmentation and the presence of drusen. In dry AMD, data suggest that hyperpigmentation in the RPE (from dysfunction in the RPE cells) followed by hypopigmentation (from the loss of RPE cells) appear before dysfunction in the photoreceptors or choriocapillaris and could be predictive for disease progression. Management of retinal diseases requires robust methods to quantify retinal melanin, specifically in the RPE. However, current techniques to image retinal melanin have limitations that prevent 3D in vivo imaging of melanin levels in the eye. For example, near-infrared autofluorescence and photoacoustic microscopy suffer from poor axial resolution that cannot resolve the RPE with respect to other structures, while polarization-sensitive optical coherence tomography has difficulty recovering accurate melanin levels due to scattering of pigment granules and a narrow dynamic range. As a result, there are currently no standard in vivo techniques to quantify melanin levels in the eye. Given the potential for melanin as an early disease marker, there is a great need for an ophthalmic imaging technique to quantify melanin levels in patients and animal models. The goal of this proposal is to develop photothermal optical coherence tomography (PT-OCT) to image and quantify melanin levels in the living human eye. PT-OCT detects optical absorbers in tissues, with similar resolution and imaging depth as OCT. The PT-OCT signal intensity is proportional to the concentration of the absorber (e.g., melanin), which allows for quantitative 3D images of melanin concentration. We have shown that PT-OCT can specifically measure melanin in the RPE of mouse and zebrafish models. Importantly, light exposure levels for PT-OCT in the eye are within safety standards and the FDA recently designated PT-OCT in the eye as a non-significant risk study. PT-OCT is advantageous for melanin imaging in the RPE because it is sensitive to small changes in pigmentation and the photothermal signal is easily quantified for robust comparisons between samples. This proposal aims to determine PT-OCT melanin sensitivity ranges and first- in-human feasibility to enable quantitative 3D imaging of melanin in the eye in vivo.
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