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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019951-04
Application #
8665940
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2013-03-12
Project End
2016-02-29
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Florida International University
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33199
Shah, Ronil S; Soetikno, Brian T; Yi, Ji et al. (2016) Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser-Induced Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci 57:OCT86-95
Li, Hao; Liu, Wenzhong; Dong, Biqin et al. (2016) J Biophotonics :
Dong, Biqin; Chen, Siyu; Zhou, Fan et al. (2016) Real-time Functional Analysis of Inertial Microfluidic Devices via Spectral Domain Optical Coherence Tomography. Sci Rep 6:33250
Dong, Biqin; Almassalha, Luay M; Stypula-Cyrus, Yolanda et al. (2016) Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast. Proc Natl Acad Sci U S A 113:9716-21
Liu, Wenzhong; Zhang, Hao F (2016) Photoacoustic imaging of the eye: A mini review. Photoacoustics 4:112-123
Childs, Andre; Li, Hao; Lewittes, Daniella M et al. (2016) Fabricating customized hydrogel contact lens. Sci Rep 6:34905
Urban, Ben E; Dong, Biqin; Nguyen, The-Quyen et al. (2016) Subsurface Super-resolution Imaging of Unstained Polymer Nanostructures. Sci Rep 6:28156
Dong, Biqin; Almassalha, Luay; Urban, Ben E et al. (2016) Super-resolution spectroscopic microscopy via photon localization. Nat Commun 7:12290
Chen, Siyu; Shu, Xiao; Yi, Ji et al. (2016) Dual-band optical coherence tomography using a single supercontinuum laser source. J Biomed Opt 21:66013
Liu, Wenzhong; Li, Hao; Shah, Ronil S et al. (2015) Simultaneous optical coherence tomography angiography and fluorescein angiography in rodents with normal retina and laser-induced choroidal neovascularization. Opt Lett 40:5782-5

Showing the most recent 10 out of 52 publications