Effect of neurosteroids on the retinal gabaergic system and electroretinographic activity in the golden hamster

Abstract

It has been established that neurosteroids can either inhibit or enhance GABA A receptor activity. Although GABA is the main inhibitory neurotransmitter in the mammalian retina, the effects of neurosteroids on retinal GABAergic activity have not been investigated. dependent, as in its absence release was not altered. The intravitreal injection of pregnenolone sulfate or vigabatrin (an irreversible inhibitor of GABA degradation) significantly decreased scotopic b-wave amplitude, whereas the opposite effect was evident when bicuculline or allotetrahydrodeoxycorticosterone were injected. A protein with a molecular weight close to that of hamster adrenal cytochrome P450 side-chain cleavage (P450scc) was detected in the hamster retina. P450scc-like immunoreactivity was localized in the inner nuclear and the ganglion cell layers. These results indicate that neurosteroids significantly modulate retinal GABAergic neurotransmission and electroretinographic activity. In addition, the selective localization of P450scc suggests that neurosteroid biosynthesis might occur only in some layers of the hamster retina.

Abnormal vascularization in mouse retina with dysregulated retinal cholesterol homeostasis

“…CYP11A1 resides along with CYP27A1 in the mitochondria of cells in the GCL and INL (70)(71)(72) and likely competes with CYP27A1 for utilization of cholesterol (73). Retinal levels of 7-ketocholesterol, a product of nonenzymatic cholesterol oxidation, are also increased in Cyp27a1 -/-retina, suggesting that 7-ketocholesterol is metabolized, at least in part, by CYP27A1, in agreement with our previous studies (74).…”

The estrogenic retina: The potential contribution to healthy aging and age-related neurodegenerative diseases of the retina

“…The vast majority of retinal synapses use glutamate for the light transmission along retinal layers, and GABA and glycine for the lateral inhibition; other neurotransmitters and many neuromodulators, perhaps including some neuroactive steroids [23], cooperate for the control of the visual pathway.…”

“…The expression of one enzyme instead of another in specific subsets of retinal cells insinuates the need for selective neurosteroid functions at specific sites in an autocrine and/or paracrine context; for example, the expression of aromatase in photoreceptors and RPE might be part of a fine regulatory circuit for the maintenance of the intra/paracrine oestrogenic milieu in the eye cup. On compelling evidence on the role of brain steroids as neuroactive agents directly modulating NMDA receptors, GABA A receptors and sigma receptors [23,[57][58][59][60], the neuroactive steroids such as pregnenolone and its sulphate, allopregnanolone, THDOC, DHT, and E2 are among those produced in the retina and so potential modulators of retinal synaptic function and survival [23,61].…”

Therapeutic Effect of Melatonin in Experimental Uveitis

“…41 After 6 hours of dark adaptation, hamsters were anesthetized with ketamine and xylazine under dim red illumination. Phenylephrine hydrochloride (2.5%) and 1% tropicamide (Alcon Laboratories, Buenos Aires, Argentina) were used to dilate the pupils, and the cornea was intermittently irrigated with balanced salt solution (Alcon Laboratories, Buenos Aires, Argentina) to maintain the baseline recording and to prevent keratopathy.…”