Purchase this article with an account.
G.A. Pinzon–Duarte, V. Denes, G.H. Daly, M. Koch, D.D. Hunter, W.J. Brunken; ß2–/–3–/– Laminin Deletion Causes Defective Development of Muller Cells And Retinal Vasculature . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2796.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Müller cells (MCs) secrete and respond to laminins and they are associated with blood vessel development and proliferation in disease. Here, we have examined the effect of the deletion of the laminins containing the ß2 and γ3 chains on MCs and vascular development.
Retinas from control, ß2–/–, γ3–/–, and dual ß2–/–γ3–/– mice were collected on postnatal days 5, 10, 15 and 20. Retinas were examined with anatomical methods. Vimentin and glutamine synthetase (GS) were used as markers of MC maturation and nidogen of vascular basement membranes (BM).
Laminin deletion disrupts MC development; the most dramatic change is in the ß2–/–γ3–/– mouse. Their processes are irregular and hypertrophic in the outer nuclear layer; they expand into the subretinal space. Perhaps the most dramatic phenotype is at the attachment point of the MC on the inner limiting membrane (ILM). Normally, MCs terminate at the ILM proximal to the ganglion cell layer. There are several different aberrant endings in the ß2–/–γ3–/– null: MCs fall short of the ILM; some end as a disorganized tangle around ectopic blood vessels; others penetrate into the vitreous body. Normally, the first GS positive cells appear at P5; in ß2–/–γ3–/– retina, GS expression was delayed by 2 days and never reached the intensity of the staining observed in control retinas of any age examined. A graded expression in GS staining was observed at P20, stronger centrally than peripherally. Another parallel disruption of the ß2–/–γ3–/– retina, is in capillary development. Nidogen, expressed in blood vessel BM, is decreased in the peripheral retina relative to the central retina. In contrast, nidogen was uniformly expressed in major vitreal vessels. In whole mount preparations, the capillary bed was observed covering only about two thirds of the retina, with a complete lack of vessels in the most peripheral retina. Finally, a disorganized, persistent intravitreal vascular network, corresponding to the hyaloid vasculature, was present.
These data suggest that the deletion of all laminin isoforms containing either ß2 or γ3 result in abnormal MC maturation, and a concomitant disruption in the development of the intra–retinal vascular network and failure in the regression of the hyaloid vessels. Although the molecular mechanisms that control blood vessel formation in retinal development and disease are not well understood, we hypothesize that Müller cell/laminin BM interactions are key regulatory steps in these processes.
This PDF is available to Subscribers Only