Nestin Expression in the Adult Mouse Retina with Pharmaceutically Induced Retinal Degeneration

Moon, Chang-Hyun; Cho, Heeyoon; Kim, Yoon Kyung; Park, Tae Kwann

doi:10.3346/jkms.2017.32.2.343

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…Nestin positive cells in the adult human retina show morphological and geographical similarity to neurons, including retinal ganglion cells, other neurons, and MG cells [35, 36]. An upregulation of Nestin expression in the retinal microglia, macrophages, and MG cells has been shown before in adult mice undergoing pharmaceutical induction of retinal degeneration, implicating that Nestin may be used as an early-stage marker of acute retinal injury [37]. Following injury, however, microglial cells become activated and express Nestin, which appears to be the cells in some of the cells in our detached neuroretina.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

et al. 2019

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Purpose Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment. Methods 12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin). Results OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer—their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo , the SRF doubled their capacity for engulfing dying RPEs. Conclusions Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.

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Section: Discussionmentioning

confidence: 99%

Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

et al. 2019

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“…Müller cells express nestin after acute injury, such as laser photocoagulation or pharmaceutically induced retinal degeneration. Similarly, astrocytes express nestin during experimental retinal detachment in rats [56,57]. Our data suggest that nestin is distinctively upregulated in the RPE layer, but not in the sensory retina.…”

Section: Discussionmentioning

confidence: 63%

Characterization of Macroglia Response during Tissue Repair in a Laser-Induced Model of Retinal Degeneration

Jahnke,

Zandi,

Elhelbawi

et al. 2023

IJMS

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Reactive gliosis is a hallmark of chronic degenerative diseases of the retina. As gliosis involves macroglia, we investigated their gliotic response to determine the role of S100β and intermediate filaments (IFs) GFAP, vimentin, and nestin during tissue repair in a laser-induced model of retinal degeneration. We validated the results with human retinal donor samples. Experiments were performed in zebrafish and mice using an argon laser (532 nm) to induce focal lesions in the outer retina. At different time points following injury induction, the kinetics of retinal degeneration and regeneration were assessed using hematoxylin and eosin staining (H&E). Immunofluorescence was performed to evaluate Müller cell (GS) and astrocyte (GFAP) injury response and to distinguish between both cell types. Additionally, staining was performed in human retinal sections containing drusen. Focal laser treatment elevated the expression of gliotic markers in the area of the damage, which was associated with increased expression of S100β, GFAP, vimentin, and nestin in mice and humans. In zebrafish, we detected S100β at the first time point, but not GFAP or nestin. Double-positive cells with the selected glia markers were detected in all models. However, in zebrafish, no double-positive GFAP/GS cells were found on days 10 and 17, nor were S100β/GS double-positive cells found on day 12. Macroglia cells showed a different pattern in the expression of IFs in degenerative and regenerative models. In particular, S100β may prove to be a target for suppressing chronic gliosis in retinal degeneration.

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“…Similarly, fewer progenitor cells are present in the adult retina [ 34 , 35 ]. In the retina of normal adult mice, Nestin is rarely expressed except for some vascular profiles in the outer plexiform layer (OPL) [ 36 , 37 ]. Therefore, re-expression of Gata3 does not induce neurogenesis but activates apoptosis in the adult retina ( Figure 7 ).…”

Section: Discussionmentioning

confidence: 99%

Gata3 Silencing Is Involved in Neuronal Differentiation and Its Abnormal Expression Impedes Neural Activity in Adult Retinal Neurocytes

Chen

Liu

et al. 2022

IJMS

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GATA binding protein 3 (Gata3), a zinc-finger transcription factor, plays an important role in neural development. However, its expression and bioactivity in the retina remain unclear. In the present study, our data indicated that Gata3 maintains the precursor state of 661W cells, and Gata3 silencing induces cell differentiation. The expression of Nestin, a marker of precursor cells, was significantly decreased in parallel, whereas the expression of Map2, a marker of differentiated neurons, was significantly increased following the decrease in Gata3. Neurite outgrowth was increased by 2.78-fold in Gata3-silenced cells. Moreover, Gata3 expression generally paralleled that of Nestin in developing mouse retinas. Both Gata3 and Nestin were expressed in the retina at postnatal day 1 and silenced in the adult mouse retina. Exogenous Gata3 significantly inhibited the neural activity of primary retinal neurocytes (postnatal day 1) by decreasing synaptophysin levels, neurite outgrowth, and cell viability. Furthermore, in vivo, exogenous Gata3 significantly induced apoptosis and the contraction of retinal outlay filaments and decreased the a- and b-waves in adult mouse intravitreal injected with AAV-Re-Gata3-T2A-GFP. Thus, Gata3 silencing promotes neuronal differentiation and neurite outgrowth. Its abnormal expression impedes neural activity in adult retinal neurocytes. This study provides new insights into Gata3 bioactivity in retinal neurocytes.

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Nestin Expression in the Adult Mouse Retina with Pharmaceutically Induced Retinal Degeneration

Cited by 9 publications

References 19 publications

Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

Clinical and molecular markers in retinal detachment—From hyperreflective points to stem cells and inflammation

Characterization of Macroglia Response during Tissue Repair in a Laser-Induced Model of Retinal Degeneration

Gata3 Silencing Is Involved in Neuronal Differentiation and Its Abnormal Expression Impedes Neural Activity in Adult Retinal Neurocytes

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