Subnormal retinal oxygenation response precedes diabetic-like retinopathy.
OBJECTIVE
Determining which patients are at risk for the development of diabetic retinopathy is expected to greatly improve existing prevention and treatment options. In this study, using an animal model of diabetic retinopathy, the hypothesis was tested that magnetic resonance imaging (MRI) and a carbogen inhalation challenge provides important diagnostic information regarding the risk of developing diabetic retinopathy.


METHODS
MRI was used to measure noninvasively the change in oxygen tension along the entire inner retina (i.e., from superior ora serrata to inferior ora serrata) during a carbogen (95% O2/5% CO2) inhalation challenge (IOVS 1996;37:2089). Two animal groups were examined by this MRI method at two time points: (1) rats fed either normal rat chow (n = 20) or a 50% galactose diet (n = 20) for 3.5 months (i.e., before the appearance of extensive retinal lesions) or (2) rats fed either normal rat chow (n = 3) for 15 months or a 30% galactose diet (n = 4) for 15 to 18 months (i.e., when lesions are present). Retinal biochemical and morphometric measurements were also obtained.


RESULTS
After 3.5 months of galactosemia, before the appearance of extensive retinal morphologic lesions, a significant (P < 0.05) reduction in the panretinal oxygenation response was observed in the galactosemic group compared with its age-matched control. These galactose-fed animals also displayed a significantly (P < 0.05) larger oxygenation response in the inferior hemiretina than in the superior hemiretina. After 15 to 18 months of galactosemia, during the period when lesions are present, the panretinal oxygenation response remained significantly (P < 0.05) lower in the galactose-fed animals than in their age-matched controls. In contrast to the 3.5-month results, the oxygenation response in galactosemic animals at 15 to 18 months was significantly (P < 0.05) larger in the superior than in the inferior hemiretina. Hemiretinal oxygenation responses were not different in normal controls at either duration.


CONCLUSIONS
MRI measurement of the retinal oxygenation response to a carbogen challenge appears to be a powerful new and noninvasive approach that may be useful for assessing aspects of pathophysiology underlying the development of diabetic retinopathy in galactosemic rats. These results support our working hypothesis and suggest that further research into the diagnostic potential of this MRI approach for predicting the development of diabetic retinopathy is warranted.
Berkowitz
B A
BA
Department of Anatomy and Cell Biology, Kresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA.
Kowluru
R A
RA
Frank
R N
RN
Kern
T S
TS
Hohman
T C
TC
Prakash
M
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000008:administration & dosage; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D005632:Fructose / Q000097:blood; D004376:Galactitol / Q000097:blood; D005690:Galactose / Q000008:administration & dosage; D005693:Galactosemias / Q000209:etiology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007294:Inositol / Q000097:blood; D008279:Magnetic Resonance Imaging; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism*; D010313:Partial Pressure; D051381:Rats; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D013012:Sorbitol / Q000097:blood
D001786:Blood Glucose; D004376:Galactitol; D002245:Carbon Dioxide; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; C011700:carbogen; D005947:Glucose; D010100:Oxygen; D005690:Galactose