Diabetic retinopathy (DR) is a leading cause of irreversible blindness among working-age adults, which is a typical type of ischemia driven retinal disease characterized by microvascular damage to the retina in patients with diabetes. DR progresses through a sequence of recognizable stages, which begin with structural and functional derangement of the retinal microcirculation even before the early clinical signs occur. The earliest clinical signs of DR are microaneurysms and dot intraretinal hemorrhages resulting from damage to the capillary pericytes and endothelial cells. This capillary damage leads to an increase in retinal vascular permeability, localized loss of capillaries with resulting ischemia, and, in the final stage of DR, the growth of abnormal retinal blood vessels (pathological retinal neovascularization) known as proliferative diabetic retinopathy (PDR). Our long term goal is to provide clinical comprehensive functional and anatomical assessment of retinal vessels in humans. In the proposed project, we first address the need for technology by developing multimodal technologies based on functional photoacoustic ophthalmoscopy (PAOM), optical coherence tomography (OCT)/optical Doppler tomography (ODT). The multimodal imaging technology will be validated and optimized through imaging animal models. Then we will test the hypothesis that the multimodal imaging technology based on PAOM and OCT/ODT can provide comprehensive functional information for the early diagnosis of DR before clinical signs occur in the oxygen induced retinopathy (OIR) rat model. To further test the hypothesis we will apply intervention at the hemodynamic threshold (the earliest hemodynamic changes signifying DR) found by the proposed imaging system on the OIR rat model to show the early intervention benefits - after the time point of hemodynamic threshold interventions cannot prevent PDR.
Aim 1. Develop a PAOM to measure sO2 in retinal vessels. PAOM provides accurate quantification of sO2 in retinal vessels by directly sensing the different optical absorption of oxy- and deoxy-hemoglobins. A powerless contact lens integrated with an ultrasonic transducer will be developed for imaging the eye.
Aim 2. Develop a dual beam spectral domain OCT to image retinal hemodynamics. The OCT system features two probing beams separated by a controlled distance on retina. Thus, effects of the Doppler angle in blood flow measurement are eliminated and the absolute blood flow velocity can be measured in real-time.
Aim 3. Integrate POAM and OCT to provide multimodal functional imaging of both sO2 and blood flow of retinal blood vessels. Validate and optimize the integrated system by imaging phantoms and the eyes of normal rats and rabbits.
Aim 4. Test the hypothesis using the developed technology by studying the variation of retinal vascular functions during ischemic retinopathy development in the OIR rat model.

Public Health Relevance

The proposed research will provide a powerful multimodal functional retinal imaging tool that enables the early diagnosis of diabetic retinopathy before clinical signs occur. It also provides a unique tool for the research on the pathological pathways of diabetic retinopathy and the development of new therapies.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Florida International University
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
Zip Code
Liu, Wenzhong; Schultz, Kathryn M; Zhang, Kevin et al. (2014) In vivo corneal neovascularization imaging by optical-resolution photoacoustic microscopy. Photoacoustics 2:81-86
Ma, Teng; Zhang, Xiangyang; Chiu, Chi Tat et al. (2014) Systematic study of high-frequency ultrasonic transducer design for laser-scanning photoacoustic ophthalmoscopy. J Biomed Opt 19:16015
Song, Wei; Wei, Qing; Liu, Wenzhong et al. (2014) A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography. Sci Rep 4:6525
Chou, Jonathan; Rollins, Stuart; Fawzi, Amani A (2014) Role of endothelial cell and pericyte dysfunction in diabetic retinopathy: review of techniques in rodent models. Adv Exp Med Biol 801:669-75
Fawzi, Amani A; Chou, Jonathan C; Kim, Gina A et al. (2014) Sildenafil attenuates vaso-obliteration and neovascularization in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 55:1493-501
Chou, Jonathan C; Rollins, Stuart D; Ye, Minghao et al. (2014) Endothelin receptor-A antagonist attenuates retinal vascular and neuroretinal pathology in diabetic mice. Invest Ophthalmol Vis Sci 55:2516-25
Urban, Ben E; Yi, Ji; Yakovlev, Vladislav et al. (2014) Investigating femtosecond-laser-induced two-photon photoacoustic generation. J Biomed Opt 19:085001
Li, Hao; Dong, Biqin; Zhang, Zhen et al. (2014) A transparent broadband ultrasonic detector based on an optical micro-ring resonator for photoacoustic microscopy. Sci Rep 4:4496
Dong, Biqin; Chen, Siyu; Zhang, Zhen et al. (2014) Photoacoustic probe using a microring resonator ultrasonic sensor for endoscopic applications. Opt Lett 39:4372-5
Liu, Wenzhong; Liu, Tan; Song, Wei et al. (2013) Automatic retinal vessel segmentation based on active contours method in Doppler spectral-domain optical coherence tomography. J Biomed Opt 18:16002

Showing the most recent 10 out of 19 publications