Differential expression of three glutamate transporter subtypes in the rat retina

Abstract

The immunocytochemical distribution of the three excitatory amino acid transporter subtypes GLT-1, GLAST-1 and EAAC-1 was studied in the rat retina using antibodies raised against synthetic peptides corresponding to the C-terminus of each transporter subtype (Rothstein et al. 1994). A comparative immunoblot analysis of rat cortex, cerebellum and retina membrane proteins suggested the following rank order of glutamate transporter subtype expression in retina: GLAST-1>/=EAAC-1>GLT-1. GLAST-1 immunoreactivity was seen in Müller cells and astrocytes. EAAC-1 was found in horizontal cells, in amacrine and displaced amacrine cells, and in ganglion cells. A minority of bipolar cells also expressed EAAC-1. GLT-1 was preferentially expressed by different types of bipolar cells; however, it was also found in some amacrine cells. The functional role of this differential distribution of glutamate transporters in the retina is discussed.

Glutamate uptake in retinal glial cells during diabetes

“…Figure 1a and b show vertical cryostat sections of control and diabetic rat retinae following 12 weeks of diabetes that had been immunolabelled for GLAST. Consistent with previous reports, GLAST was localised within Müller cell processes within both plexiform layers and their endfeet in the inner limiting membrane [13,21]. We were unable to detect any large differences in immunoreactivity between control and diabetic retinae.…”

“…There are two major classes of macroglial cells within the retina; Müller cells are the predominant glial cell type and express the glutamate transporter GLAST [8,13,21]. It is well known that GLAST provides the bulk of glutamate uptake within the retina [23,24,38].…”

“…Astrocytes are intricately linked with the vasculature and have processes within the nerve fibre and ganglion cell layers [12]. The function of astrocytes within the retina is not clearly defined, although they do express glutamate transporters such as GLAST and EAAT4 [13,14]. Highlighting the potential importance of these glutamate transporters in retinal pathology, studies have reported increased glutamate concentrations within the vitreous of patients with diabetes and in diabetic retinae [15,16].…”

“…In order to maintain normal retinal function, glutamate must be removed rapidly from the synaptic cleft. At the molecular level, five glutamate transporters have been cloned: excitatory amino acid transporters (EAAT) 1-5, all of which have been identified in the retina [13,14,[18][19][20][21][22]. Although the function of specific transporter types is contentious, it is clear that GLAST (EAAT1) is the predominant transporter for removal of glutamate within the retina and defects in its function lead to major deleterious effects on vision [20,23,24].…”

The upregulation of GLAST-1 is an indirect antiapoptotic mechanism of GDNF and neurturin in the adult CNS

“…In the mammalian retina, GLAST-1 is localized to Mü ller glia and nerve fiber layer astrocytes. [14][15][16] GLAST-1 inhibition or deficiency has been shown to increase glutamate levels in the eye and promote RGC degeneration. 17 has been localized to cone photoreceptors and cone bipolar cells in the mammalian retina.…”