Noninvasive imaging of retinal morphology and microvasculature in obese mice using optical coherence tomography and optical microangiography.
OBJECTIVE
To evaluate early diabetes-induced changes in retinal thickness and microvasculature in a type 2 diabetic mouse model by using optical coherence tomography (OCT)/optical microangiography (OMAG).


METHODS
Twenty-two-week-old obese (OB) BTBR mice (n = 10) and wild-type (WT) control mice (n = 10) were imaged. Three-dimensional (3D) data volumes were captured with spectral domain OCT using an ultrahigh-sensitive OMAG scanning protocol for 3D volumetric angiography of the retina and dense A-scan protocol for measurement of the total retinal blood flow (RBF) rate. The thicknesses of the nerve fiber layer (NFL) and that of the NFL to the inner plexiform layer (IPL) were measured and compared between OB and WT mice. The linear capillary densities within intermediate and deep capillary layers were determined by the number of capillaries crossing a 500-μm line. The RBF rate was evaluated using an en face Doppler approach. These quantitative measurements were compared between OB and WT mice.


RESULTS
The retinal thickness of the NFL to IPL was significantly reduced in OB mice (P < 0.01) compared to that in WT mice, whereas the NFL thickness between the two was unchanged. 3D depth-resolved OMAG angiography revealed the first in vivo 3D model of mouse retinal microcirculation. Although no obvious differences in capillary vessel densities of the intermediate and deep capillary layers were detected between normal and OB mice, the total RBF rate was significantly lower (P < 0.05) in OB mice than in WT mice.


CONCLUSIONS
We conclude that OB BTBR mice have significantly reduced NFL-IPL thicknesses and total RBF rates compared with those of WT mice, as imaged by OCT/OMAG. OMAG provides an unprecedented capability for high-resolution depth-resolved imaging of mouse retinal vessels and blood flow that may play a pivotal role in providing a noninvasive method for detecting early microvascular changes in patients with diabetic retinopathy.
Department of Bioengineering, University of Washington, Seattle, Washington.
Zhongwei
Z
Zhi
Jennifer R
JR
Chao
Tomasz
T
Wietecha
Kelly L
KL
Hudkins
Charles E
CE
Alpers
Ruikang K
RK
Wang
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005451:Fluorescein Angiography; D021621:Imaging, Three-Dimensional / Q000379:methods; D051379:Mice; D008820:Mice, Obese; D012039:Regional Blood Flow / Q000502:physiology; D012160:Retina / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*; D041623:Tomography, Optical Coherence
obesity; optical coherence tomography; retinal microcirculation; retinal vasculature