Background: Macular degeneration (MD) is one of the most frequent causes of visual deficit, resulting in alterations affecting not only the retina but also the entire visual pathway up to the brain areas. This would seem related not just to signal deprivation but also to a compensatory neuronal reorganization, having significant implications in terms of potential rehabilitation of the patient and therapeutic perspectives. Objective: This paper aimed to outline, by analyzing the existing literature, the current understanding of brain structural and functional changes detected with neuroimaging techniques in subjects affected by juvenile and age-related maculopathy. Methods: Articles using various typologies of central nervous system (CNS) imaging in at least six patients affected by juvenile or age-related maculopathy were considered. A total of 142 were initially screened. Non-pertinent articles and duplicates were rejected. Finally, 19 articles, including 649 patients, were identified. Results: In these sources, both structural and functional modifications were found in MD subjects' CNS. Changes in visual cortex gray matter volume were observed in both age-related MD (AMD) and juvenile MD (JMD); in particular, an involvement of not only its posterior part but also the anterior one suggests further causes besides an input-deprivation mechanism only. White matter degeneration was also found, more severe in JMD than in AMD. Moreover, functional analysis revealed differences in cortical activation patterns between MD and controls, suggesting neuronal circuit reorganization. Interestingly, attention and oculomotor training allowed better visual performances and correlated to a stronger cortical activation, even of the area normally receiving inputs from lesioned macula. Conclusion: In MD, structural and functional changes in cerebral circuits and visual pathway can happen, involving both cerebral volume and activation patterns. These modifications, possibly due to neuronal plasticity (already observed and described for several brain areas), can allow patients to compensate for macular damage and gives therapeutic perspectives which could be achievable through an association between oculomotor training and biochemical stimulation of neuronal plasticity.
Glaucoma and macular degeneration are leading causes of irreversible blindness, significantly compromising the quality of life and having a high economic and social impact. Promising therapeutic approaches aimed at regenerating or bypassing the damaged anatomical-functional components are currently under development: these approaches have generated great expectations, but to be effective require a visual network that, despite the pathology, maintains its integrity up to the higher brain areas. In the light of this, the existing findings concerning how the central nervous system modifies its connections following the pathological damage caused by glaucoma and macular degeneration acquire great interest. This review aims to examine the scientific literature concerning the morphological and functional changes affecting the central nervous system in these pathological conditions, summarizing the evidence in an analytical way, discussing their possible causes and highlighting the potential repercussions on the current therapeutic perspectives.
Phosphatidic acid (PA) produced by phospholipase D1 has been shown to contribute to secretory vesicle exocytosis in a large number of cell models. Among various hypotheses, PA may contribute to recruit and/or activate at the exocytotic site a set of proteins from the molecular machinery dedicated to secretion, but also directly influence membrane curvature thereby favoring membrane rearrangements required for membrane fusion. The release of informative molecules by regulated exocytosis is a tightly controlled process. It is thus expected that PA produced to trigger membrane fusion should be rapidly metabolized and converted in a lipid that does not present similar characteristics. PA‐phosphatases of the lipin family are possible candidates as they convert PA into diacylglycerol. We show here that lipin 1 and lipin 2 are expressed in neuroendocrine cells where they are cytosolic, but also partially associated with the endoplasmic reticulum. Silencing of lipin 1 or 2 did not affect significantly either basal or evoked secretion from PC12 cells, suggesting that it is unlikely that conversion of PA into a secondary lipid by lipins might represent a regulatory step in exocytosis in neurosecretory cells. However, in agreement with a model in which PA‐metabolism could contribute to prevent entering into exocytosis of additional secretory vesicles, ectopic expression of lipin1B‐GFP in bovine chromaffin cells reduced the number of exocytotic events as revealed by carbon fiber amperometry recording. Furthermore, individual spike parameters reflecting fusion pore dynamics were also modified by lipin1B‐GFP, suggesting that a tight control of PA levels represents an important regulatory step of the number and kinetic of exocytotic events.
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