In vivo assessment of retinal vascular wall dimensions.
OBJECTIVE
Retinal blood vessel diameter and arteriovenous ratio (AVR) are commonly used diagnostic parameters. Because vascular walls are typically not visible in funduscopy, clinical AVR estimation is based on the lumen rather than the entire vessel diameter. Here the authors used a transgenic mouse model to quantify AVR in vivo based on total vessel dimensions (wall and lumen).


METHODS
Confocal scanning laser ophthalmoscopy (cSLO) and indocyanine green angiography of the retinal vasculature were performed in wild-type and transgenic mice expressing green fluorescent protein (GFP) under the transcriptional control of the smooth muscle type α-actin (αSMA) promoter. Spectral-domain-OCT and ERG were performed to control for integrity of retinal structure and function in vivo and histology to demonstrate the location of GFP expression.


RESULTS
Native cSLO imaging and angiography yielded only inner vessel diameters similar to those observed through clinical funduscopy. In αSMA-GFP mice, autofluorescence imaging of the GFP-marked vascular walls also allowed the determination of outer vessel diameters. The mean AVR based on either inner diameter (AVR(id) = 0.72 ± 0.08) or outer diameter (AVR(od) = 0.97 ± 0.09) measurements were significantly different (P < 0.01).


CONCLUSIONS
Transgenic αSMA-GFP expression in murine vessel wall components allowed quantification of retinal vessel outer diameters in vivo. Although arterioles and venules differ in lumen and vessel wall width, they share a common outer diameter, leading to an AVR(od) close to unity. Because vessel walls are primary targets in common hypertensive and metabolic diseases, αSMA-GFP transgenic mice may prove valuable in the detailed assessment of such disorders in vivo.
Fischer
M Dominik
MD
Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. dominik.fischer@med.uni-tuebingen.de
Huber
Gesine
G
Feng
Yuxi
Y
Tanimoto
Naoyuki
N
Mühlfriedel
Regine
R
Beck
Susanne C
SC
Tröger
Eric
E
Kernstock
Christoph
C
Preising
Markus N
MN
Lorenz
Birgit
B
Hammes
Hans Peter
HP
Seeliger
Mathias W
MW
D000199:Actins / Q000378:metabolism; D000818:Animals; D001837:Body Weights and Measures; D004396:Coloring Agents; D004596:Electroretinography; D005451:Fluorescein Angiography; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007208:Indocyanine Green; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009887:Ophthalmoscopy; D012161:Retinal Artery / Q000033:anatomy & histology* / Q000378:metabolism; D012169:Retinal Vein / Q000033:anatomy & histology* / Q000378:metabolism; D041623:Tomography, Optical Coherence
D000199:Actins; D004396:Coloring Agents; C544013:alpha-smooth muscle actin, mouse; D049452:Green Fluorescent Proteins; D007208:Indocyanine Green