Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model.

The active component of Wolfberry (Lycium barbarum), lycium barbarum polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion cells (RGCs) against ocular hypertension (OH). Aiming to study whether this neuroprotection is mediated via modulating immune cells in the retina, we used multiphoton confocal microscopy to investigate morphological changes of microglia in whole-mounted retinas. Retinas under OH displayed slightly activated microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited moderately activated microglia in the inner retina with ramified appearance but thicker and focally enlarged processes. Intravitreous injection of lipopolysaccharide decreased the survival of RGCs at 4 weeks, and the activated microglia exhibited amoeboid appearance as fully activated phenotype. When activation of microglia was attenuated by intravitreous injection of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was attenuated. The results implicated that neuroprotective effects of LBP were partly due to modulating the activation of microglia.

Erratum: Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model.

The active component of Wolfberry (Lycium barbarum), lycium barbarum polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion cells (RGCs) against ocular hypertension (OH). Aiming to study whether this neuroprotection is mediated via modulating immune cells in the retina, we used multiphoton confocal microscopy to investigate morphological changes of microglia in whole-mounted retinas. Retinas under OH displayed slightly activated microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited moderately activated microglia in the inner retina with ramified appearance but thicker and focally enlarged processes. Intravitreous injection of bacterial endotoxin lipopolysaccharide (LPS) decreased the survival of RGCs at 4 weeks, and the activated microglia exhibited amoeboid appearance as fully activated phenotype. When activation of microglia was attenuated by intravitreous injection of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was attenuated. The results implicated that neuroprotective effects of LBP were partly due to modulating the activation of microglia.[This corrects the article on p. in vol. .].

Mechanisms for gonadotropin-releasing hormone potentiation of growth hormone rebound following norepinephrine inhibition in goldfish pituitary cells.

In the goldfish, norepinephrine (NE) inhibits growth hormone (GH) secretion through activation of pituitary alpha(2)-adrenergic receptors. Interestingly, a GH rebound is observed after NE withdrawal, which can be markedly enhanced by prior exposure to gonadotropin-releasing hormone (GnRH). Here we examined the mechanisms responsible for GnRH potentiation of this "postinhibition" GH rebound. In goldfish pituitary cells, alpha(2)-adrenergic stimulation suppressed both basal and GnRH-induced GH mRNA expression, suggesting that a rise in GH synthesis induced by GnRH did not contribute to its potentiating effect. Using a column perifusion approach, GnRH given during NE treatment consistently enhanced the GH rebound following NE withdrawal. This potentiating effect was mimicked by activation of PKC and adenylate cyclase (AC) but not by induction of Ca(2+) entry through voltage-sensitive Ca(2+) channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivation of PKC, removal of extracellular Ca(2+), blockade of VSCC, and inhibition of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). Inactivation of AC and PKA, however, was not effective in this regard. These results, as a whole, suggest that GnRH potentiation of GH rebound following NE inhibition is mediated by PKC coupled to Ca(2+) entry through VSCC and subsequent activation of CaMKII. Apparently, the Ca(2+)-dependent cascades are involved in GH secretion during the rebound phase but are not essential for the initiation of GnRH potentiation. Since GnRH has been previously shown to have no effects on cAMP synthesis in goldfish pituitary cells, the involvement of cAMP-dependent mechanisms in GnRH potentiation is rather unlikely.

Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma.

Glaucoma is one of the major neurological disorders in eye leading to irreversible blindness in elderly. Increase in intraocular pressure (IOP) has been considered to be the major risk factor for the progressive loss of retinal ganglion cells (RGCs) in retina. While attenuation of IOP has been a major pharmaceutical target, reduction of IOP cannot prevent progressive loss of RGCs. In this regard, urgent need for alternative treatment has to be investigated. Anti-aging medicinal herb Lycium barbarum L. has been used for centuries in Eastern World to protect the eyes and maintain good health. Using an ocular hypertension (OH) model in rat by laser photocoagulation of episcleral and limbal veins, we attempted to investigate whether L. barbarum can promote RGCs survival against elevated IOP. Oral administration of L. barbarum in Sprague-Dawley rats (250-280 g) significantly reduced the loss of RGCs, although elevated IOP was not significantly altered. Rats fed with the 1 mg/kg extract could nearly totally escape from pressure-induced loss of RGCs. In conclusion, this is the first in vivo report showing the therapeutic function of L. barbarum against neurodegeneration in the retina of rat OH model. The results demonstrate that this extract may be a potential candidate for the development of neuroprotective drug against the loss of RGCs in glaucoma.