Multimodal assessment of photoreceptor structure and function in retinal trauma

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PROJECT SUMMARY Rod and cone photoreceptors initiate vision by converting light into an electrical signal via phototransduction. Many conditions either directly or indirectly prohibit photoreceptor function, including inherited retinal conditions, systemic diseases, neurological disorders, and traumatic injuries. Clinical objectives are to identify pathology, prevent future damage, and ideally restore lost function. Vision research has placed tremendous efforts on restorative vision treatments, but the technology required to accurately detect retinal changes and monitor retinal recovery remains limited in clinical settings. Visual deficits induced by retinal trauma is a common cause of vision loss that often resolves over time – providing an excellent model to characterize and improve clinical techniques for detecting retinal abnormalities and monitoring retinal restoration. Ubiquitous clinical tests to assess retinal structure and function, including optical coherence tomography (OCT), microperimetry, and best-corrected visual acuity (BCVA), are low resolution and/or subjective. There is thus a critical need to improve biomarkers for detection of retinal pathology and application of novel approaches for better understanding behind the pathophysiology of traumatic vision loss and retinal recovery. In this project, adaptive optics scanning light ophthalmoscopy (AOSLO) – a technique enabling high-resolution in vivo imaging and functional assessment of photoreceptors – will be utilized to assess the relationship between AO-based photoreceptor metrics and clinically used tools. Our central hypothesis is that multi-modal assessment of photoreceptor structure and function will reveal variations in photoreceptor metrics that can be translated into biomarkers for the status and function of the healthy and diseased retina. The first specific aim is to identify cellular correlates of cone photoreceptor biomarkers from clinical tools. Specifically, we will use AOSLO to examine conventional clinical tools, OCT and microperimetry. The second specific aim is to assess cone photoreceptor structure in individuals with mild traumatic brain injury (TBI). Visual dysfunction is commonly reported following mild TBI with no clinical ophthalmic findings. We hypothesize that individuals with a clinical diagnosis of mild TBI and subsequent visual dysfunction will have subclinical photoreceptor structural and functional abnormalities. The third specific aim is to identify the mechanism of cone photoreceptor recovery following macular hole repair. There are competing theories of visual recovery following macular hole repair, implicating either photoreceptor migration or recovery of photoreceptor outer segment structure over time. The research planned herein provides a unique individualized training opportunity by combining in vivo retinal imaging, translation between retinal and neurological disorders, optical design, software development, and biomedical engineering. This proposal creates an ideal platform to develop complementary skills required for an independent translational scientist, such as broadening my technical acumen, improving scientific communication, developing mentoring skills, and expanding my professional network.