Metabolic Analysis of Vitreous/Lens and Retina in Wild Type and Retinal Degeneration Mice

Murenu, Elisa; Kostidis, Sarantos; Lahiri, Shibojyoti; Geserich, Anna S.; Imhof, Axel; Giera, Martin; Michalakis, Stylianos

doi:10.3390/ijms22052345

Cited by 7 publications

(4 citation statements)

References 77 publications

(73 reference statements)

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“…Similar results hinting at a neuroprotective role of microglia were obtained in a mouse model of retinal detachment ( 176 ) and of excitotoxicity ( 177 ). Interestingly, signs of excitotoxicity were also found in Pde6b rd1 mutants, possibly justifying similar microglia responses in different degenerative contexts ( 158 , 178 ).…”

Section: Roles Of Microglia In Pathologymentioning

confidence: 98%

“…Early RP is characterized by progressive loss of rod photoreceptors. As discussed in the opening of this chapter, the loss of photoreceptors per se deprives microglia of signals important for their homeostasis, though sudden hyperoxidative environment, oxidative stress and alteration of retinal metabolism may also concur to foster and sustain microglial response (155)(156)(157)(158)(159)(160). Similar to what happens throughout the CNS, retinal microglia usually respond by adopting an amoeboid morphology and migrating to the area of insult, ultimately proliferating to amplify their numbers and acting to resolve the ongoing degeneration.…”

Section: Retinitis Pigmentosamentioning

confidence: 99%

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More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. While most knowledge about microglia comes from brain studies, some mechanisms have been confirmed for microglia cells in the retina, the light-sensing compartment of the eye responsible for initial processing of visual information. However, several key pieces of this puzzle are still unaccounted for, as the characterization of retinal microglia has long been hindered by the reduced population size within the retina as well as the previous lack of technologies enabling single-cell analyses. Accumulating evidence indicates that the same cell type may harbor a high degree of transcriptional, morphological and functional differences depending on its location within the central nervous system. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important. Here, we review the current understanding of retinal microglia cells in physiology and in disease, with particular emphasis on newly discovered mechanisms and future research directions.

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Section: Roles Of Microglia In Pathologymentioning

confidence: 98%

Section: Retinitis Pigmentosamentioning

confidence: 99%

More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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“…This can lead to altered retinal soma size, distribution, and spontaneous activity compared to normal postnatal development 62 , 63 . As the VH serves as a metabolite reservoir for the retina while the VH and lens compositions can alter along with changes in the concentration of selected metabolites in the retina 36 , 64 , it is possible that the decrease in retinal apoptosis and metabolic demand may concur with the reduced VH and lens volumetric growth observed in the surviving eyes of our ME rats 65 . Adults who lost one eye early in life may show residual visual deficits even after prolonged monocular status 66 , yet the underlying mechanisms remain unclear.…”

Section: Discussionmentioning

confidence: 99%

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes

Kancherla

Hamade

et al. 2021

Sci Rep

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This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague–Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188–289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.

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“…Thus, it became clear that there is an imminent need for a pan-gene-mutation therapy, which galvanized investigations into disease mechanisms beyond the mutant proteins. As a result, in recent years, our research has focused on the metabolic changes caused by the absence of the native protein or the expression of a mutant protein (for example, Rtbdn −/− ( Kelley et al, 2017 ; Sinha et al, 2021 ), Rd1 ( Murenu et al, 2021 ), mutations in Prph2 ( Ding et al, 2004 ; Conley et al, 2014 ; Stuck et al, 2014 ; Stuck et al, 2016 ), or mutant Prph2/Rtbdn −/− ( Genc et al, 2020a ; Genc et al, 2020b ). After all, metabolism is the source of energy that cells need to achieve homeostasis or to execute cell death and to provide the metabolic intermediates needed for anabolic activities.…”

Section: Introductionmentioning

confidence: 99%

The Neuroprotective Role of Retbindin, a Metabolic Regulator in the Neural Retina

et al. 2022

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Dysregulation of retinal metabolism is emerging as one of the major reasons for many inherited retinal diseases (IRDs), a leading cause of blindness worldwide. Thus, the identification of a common regulator that can preserve or revert the metabolic ecosystem to homeostasis is a key step in developing a treatment for different forms of IRDs. Riboflavin (RF) and its derivatives (flavins), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are essential cofactors for a wide range of cellular metabolic processes; hence, they are particularly critical in highly metabolically active tissues such as the retina. Patients with RF deficiency (ariboflavinosis) often display poor photosensitivity resulting in impaired low-light vision. We have identified a novel retina-specific RF binding protein called retbindin (Rtbdn), which plays a key role in retaining flavin levels in the neural retina. This role is mediated by its specific localization at the interface between the neural retina and retinal pigment epithelium (RPE), which is essential for metabolite and nutrient exchange. As a consequence of this vital function, Rtbdn’s role in flavin utilization and metabolism in retinal degeneration is discussed. The principal findings are that Rtbdn helps maintain high levels of retinal flavins, and its ablation leads to an early-onset retinal metabolic dysregulation, followed by progressive degeneration of rod and cone photoreceptors. Lack of Rtbdn reduces flavin levels, forcing the neural retina to repurpose glucose to reduce the production of free radicals during ATP production. This leads to metabolic breakdown followed by retinal degeneration. Assessment of the role of Rtbdn in several preclinical retinal disease models revealed upregulation of its levels by several folds prior to and during the degenerative process. Ablation of Rtbdn in these models accelerated the rate of retinal degeneration. In agreement with these in vivo studies, we have also demonstrated that Rtbdn protects immortalized cone photoreceptor cells (661W cells) from light damage in vitro. This indicates that Rtbdn plays a neuroprotective role during retinal degeneration. Herein, we discussed the specific function of Rtbdn and its neuroprotective role in retinal metabolic homeostasis and its role in maintaining retinal health.

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Metabolic Analysis of Vitreous/Lens and Retina in Wild Type and Retinal Degeneration Mice

Cited by 7 publications

References 77 publications

More than meets the eye: The role of microglia in healthy and diseased retina

More than meets the eye: The role of microglia in healthy and diseased retina

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes

The Neuroprotective Role of Retbindin, a Metabolic Regulator in the Neural Retina

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