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2018 ICTS KL-2 Award Announcement

 

The ICTS is pleased to announce the awardee of the 2018 KL-2 Mentored Scholar Award.

This ICTS award is intended to support a two-year period of mentored career development. This award is to allow scholars to develop a solid portfolio of pilot and preliminary data suitable for competitive extramural grant applications; a robust record of publications and presentations at national scientific meetings; and a program of courses and experiential learning in areas that will advance the scholar’s proficiency in independent translational research. For more information about the ICTS program and other funded scholars visit the ICTS Website.

   

Andrew Browne, MD
Department: Ophthalmology
Mentor: Bruce Tromberg, PhD

Proposed Research
Multiphoton imaging of retinal structure and function in hypoxia
Dr. Browne proposes to develop advanced biophotonics principles in the study of oxygen dependent metabolism in retinal tissues. Oxygenation is important to both the developing and the mature retina. Pediatric retinopathy of prematurity has taught us that oxygen concentration is critical to retinal development. The majority of adult retinal pathology is comprised of retinal vascular diseases including diabetic retinopathy, retinal vein occlusion, arterial occlusion and hypertension.

   
Organoids and fish respectively provide avascular and vascular models for studying retinal oxygenation. Retinal organoids are generated from human stem cells and self-assemble into layered retinal architecture. Organoid oxygenation is entirely dependent upon oxygen concentration of the tissue culture media. Developing zebrafish tissues are dependent on diffusion mediated oxygenation from the environment. In adult fish, blood oxygenation determines retinal tissue oxygenation. These in vitro and in vivo systems allow control of oxygenation to the retinal tissues. Multiphoton microscopy to characterize intrinsic fluorophores and metabolism will be optimized to study these model systems in the context of normoxia and hypoxia. Aim 1: To determine the effect of oxygen concentration on developing retina structure and metabolism. Hypothesis 1a: Differential oxygen control during early retinal organoid development will affect inner layer metabolism and survival. Hypothesis 1b: Normal and hypoxic conditions will affect zebrafish retinal development and this will be observable by changes in the metabolic signature of developing retinal layers. Aim 2: To determine the effect of oxygen concentration on mature retina metabolism. Hypothesis 2a: Hypoxic tissue culture of mature retinal organoids will results in: (i) a detectable change in structure and metabolic signature of the retinal organoid, (ii) cell death will begin in the inner layers of the retinal organoid. Hypothesis 2b: Ischemia of adult zebrafish will result in inner retinal cell death characterized by an observable switch from oxidative phosphorylation to glycolytic metabolism.