| DIABETES VOL. 46, SUPPLEMENT 2, SEPTEMBER 1997 Growth Factor Alterations in Advanced Diabetic Retinopathy A Possible Role of Blood Retina Barrier Breakdown Andreas Pfeiffer Chronic hyperglycemia may cause growth factor
alterations that are likely to participate in tissue
remodeling typical for diabetic late complications.
However, few details of such events are known. The ocular
vitreous fluid allows studies of growth factor levels in
human eyes (after vitrectomy). The vitreous is highly
inert and protected by the blood-retina barrier and thus
probably reflects growth factor production by the normal
retina. Vitreous from patients with proliferative
diabetic retinopathy (PDR) was compared with vitreous
obtained from patients with nonproliferative eye disease
and with vitreous from patients without diabetes but with
marked neovascular proliferations due to ischemia. This
design permits us to distinguish diabetes-related from
nondiabetes-related alterations. Insulin-like growth
factor I (IGF-I), IGF-II, IGF binding protein 2
(IGFBP-2), and IGFBP-3 were elevated 3- to 13-fold in
nondiabetic retinal ischemia and 1.5- to 3-fold in PDR,
indicating that the changes were not restricted to
diabetes. These changes may partially be explained by
leakage of serum into the vitreous, since IGFs and IGFBPs
are 20- to 50-fold higher in serum than in vitreous, and
vitreous protein content was 1.5-fold elevated in PDR
subjects and 5-fold in ischemia patients compared with
control subjects. TGF-ß is a proposed antiangiogenic
factor in the eye. TGF-ß2 was the predominant
subtype in vitreous, and its total amount was not altered
in PDR patients. More importantly, the active fraction of
TGF-ß was decreased by 30 and 70% in PDR and nondiabetic
retinal ischemia patients, respectively. Since plasmin
may control TGF-ß activation, the serum protein Copyright © 1997 American Diabetes Association Last updated: 8/97 |
2-antiplasmin was measured and
found to be significantly elevated to 150 and 250% of
control values in PDR and ischemia patients,
respectively. Thus, influx of serum proteins due to
microvascular disturbances and hypoxia is proposed as a
possible cause for vitreous alterations of IGF-I and of
active TGF-ß. These changes seem to occur late in the
sequence of events leading to PDR and are not specific
for diabetes, but they were also observed in other
diseases characterized by retinal hypoxia. Diabetes
46 (Suppl. 2):S26S30, 1997