Human adipose-derived stem cells for the treatment of chemically burned rat cornea: preliminary results.

Abstract Purpose: Adipose-derived stem cells (ADSC) are multipotent, safe, non-immunogenic and can differentiate into functional keratocytes in situ. The topical use of ADSC derived from human processed lipoaspirate was investigated for treating injured rat cornea. Methods: A total of 19 rats were used. Six animals initially underwent corneal lesion experiments with 0.5 N NaOH (right eye) and 0.2 N (left). The 0.2 NaOH protocol was then used in 13 rats. All 26 eyes of 13 rats eyes received topical azythromycin bid for 3 d and divided into five treatment groups (n = 5 eyes/group), which included: control, stem cells, serum, stem + serum and adipose (raw human lipoaspirate). The four treatment groups received topical treatment three times daily for 3 d. Stem cells were isolated and harvested from human lipoaspirate. Topical eye drops were prepared daily with 1 × 10cells/treatment. Fluorescein positive defect area and light microscope assessment was performed at 20, 28, 45, 50 and 74 h. Animals were sacrificed at 74 h for histological evaluation. Data were statistically analyzed for differences amongst groups. Results: The stem cell-treated eyes had significantly smaller epithelial defects at each time point compared to control- and adipose-treated eyes (p < 0.05). This group showed slightly better epithelium healing than the serum and combined group, yet not significantly different. Histology showed that stem cell-treated corneas had complete re-epithelization, with less inflammatory cells and limited fibroblast activation structure compared with the control eyes. Conclusions: Our preliminaryresults show that topical treatment with ADSC seems to improve corneal wound healing. >>

In search of new targets for retinal neuroprotection: is there a role for autophagy?

Autophagy is a highly conserved catabolic pathway in which proteins and organelles are engulfed by vacuoles that are targeted to lysosomes for degradation. Defects in the autophagic machinery have been described in several neurodegenerative diseases uncovering the tight dependency of neuronal survival on the efficiency of the autophagic process. Despite the large amount of literature investigating autophagy in a number of pathological conditions our knowledge of its role in glaucoma neurodegeneration is just beginning. However, recent experimental data revealing thatautophagy modulation occurs in retinal ganglion cells (RGCs) under glaucoma-related stressing conditions support the hypothesis that dysfunctionalautophagy might underlie the process leading to RGC death. Although our understanding of the role of autophagy in glaucoma is still developing, there is the possibility that neuroprotection may be achieved by modulating autophagy. This would be a promising approach as it could lead to the much-sought development of alternative therapeutic strategies to prevent visual loss in glaucoma. >>

Brain involvement in glaucoma: advanced neuroimaging for understanding and monitoring a new target for therapy.

On the basis of a large body of experimental data the notion that glaucoma damages retinal ganglion cells and central areas of the visual system has been put forward. The mechanisms underlying glaucomatous involvement of the central areas are not known: the most likely hypothesis is that this event is the result of an anterograde transynaptic neurodegeneration triggered by ganglion cells' death. However, it is possible that in some cases it may be the consequence of a neurodegenerative disease of the central nervous system. In any event, novel mechanisms leading to cell demise might be implicated. The development of powerful neuroimaging techniques in conjunction with sophisticated analysis has recently provided compelling support to the involvement of central stations of the visual pathway in patients suffering of glaucoma. Diffusion Tensor-MRI allows the central damage associated with glaucoma to be assessed and therapeutic efficacy of novel neuroprotective interventions to be quantified. >>

Identification of novel pharmacological targets to minimize excitotoxic retinal damage.

Excitotoxic neuronal death is a common feature of neurodegenerative and ischemic diseases of the central nervous system (CNS) and of a variety of ocular diseases, including glaucoma. Glaucoma, one of the leading causes of blindness in the world, is characterized by a progressive degeneration of retinal ganglion cells (RGCs) and their axons and is often associated with elevated intraocular pressure (IOP). Retinal ischemia/reperfusion induced by experimental elevation of IOP leads to damage and loss of RGCs. Under these conditions, structural, functional, and biochemical changes implicate the accumulation of extracellular glutamate and activation of the excitotoxic cascade. Beside the activation of associated pathways, death of RGCs is accompanied by impaired endogenous defenses, such as the PI3K/Akt prosurvival pathway. Original neurochemical and pharmacologicalevidence are discussed here to strengthen the role for excitotoxicity in RGCs death occurring in experimental, angle closure, glaucoma in conjunction with the discovery of novel molecular targets to potentiate endogenous prosurvival defenses in the glaucomatous retina. >>