scholarly journals 1α,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Francesca Lazzara ◽  
Rosario Amato ◽  
Chiara Bianca Maria Platania ◽  
Federica Conti ◽  
Tsung-Han Chou ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Inflammatory Cytokines ◽  
Genetic Model ◽  
Ganglion Cells ◽  
Statistical Tests ◽  
Pattern Electroretinogram ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Astrocyte Activation ◽  
Age Related

Abstract Background Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice). Methods DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA. Results DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF. Conclusions 1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.

Pathways of regenerated retinotectal axons in goldfish

Development ◽  
1986 ◽  
Vol 93 (1) ◽  
pp. 1-28
Author(s):  
Claudia A. O. Stuermer
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Normal Development ◽  
Ganglion Cells ◽  
Optic Tract ◽  
Spatiotemporal Pattern ◽  
Retinal Ganglion ◽  
Retinal Axons ◽  
Age Related ◽  
Regenerated Fibres

This study investigates the order of regenerating retinal axons in the goldfish. The spatiotemporal pattern of axon regrowth was assessed by applying horseradish peroxidase (HRP) to regenerating axons in the optic tract at various times after optic nerve section and by analysing the distribution of retrogradely labelled ganglion cells in retina. At all regeneration stages labelled ganglion cells were widely distributed over the retina. There was no hint that axons from central (older) ganglion cells might regrow earlier, and peripheral (younger) ganglion cells later, as occurs in normal development. The absence of an age-related ordering in the regenerated optic nerve was demonstrated by labelling a few axon bundles intraorbitally with HRP (Easter, Rusoff & Kish, 1981) caudal to the previous cut. The retrogradely labelled cells in retina were randomly distributed in regenerates andnot clustered in annuli as in normals. Tracing regenerating axons which were stained anterogradelyfrom intraretinal HRP applications or retrogradely from single labelled tectal fascicles illustrated the fact that the regenerating axons coursed in abnormal routes in the optic nerve and tract. On the surface of the tectum regenerated fibres re-established a fascicle fan. The retinal origin of tectal fascicles was assessed by labelling individual peripheral, intermediate and rostral fascicles with HRP. The retrogradely labelled ganglion cells in the retina were often more widely distributed than in normals, but were mostly found in peripheral, intermediate and central retina, respectively. The order of fibre departure from each tectal fascicle was revealed by placing HRP either on the fascicle's proximal or on its distal half. With proximal labelling sites labelled ganglion cells were found in the temporal and nasal retina, and with distal labelling sites labelled ganglion cells were confined to nasal retina only. Further, the axonal trajectories of anterogradely labelled dorsotemporal retinal ganglion cells were compared to those of dorsonasal retinal ganglion cells in tectal whole mounts. Dorsotemporal axons were confined to the rostral tectal half, whereas dorsonasal axons followed fascicular routes into the fascicles' distal end and reached into caudal tectum. This suggests that the fibres exited along their fascicle's course in a temporonasal sequence. Thus in the tectum, fibres in fascicles restore a gross spatial and age-related order and tend to follow their normal temporonasal sequence of exit.

scholarly journals Protection of Pattern Electroretinogram and Retinal Ganglion Cells by Oncostatin M after Optic Nerve Injury

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108524 ◽  
Author(s):  
Xin Xia ◽  
Rong Wen ◽  
Tsung-Han Chou ◽  
Yiwen Li ◽  
Zhengying Wang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Injury ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pattern Electroretinogram ◽  
Oncostatin M ◽  
Retinal Ganglion ◽  
Optic Nerve Injury

scholarly journals Protective effect of endogenous apelin against age-related loss of retinal ganglion cells in mice

2020 ◽  
Vol 93 (0) ◽  
pp. 2-P-215
Author(s):  
Yuki Ishimaru ◽  
Akihide Sumino ◽  
Fumiya Shibagaki ◽  
Hikari Chitose ◽  
Reina Miura ◽  
...  
Keyword(s):  
Protective Effect ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Age Related

Age-Related Losses of Retinal Ganglion Cells and Axons

2008 ◽  
Vol 49 (10) ◽  
pp. 4437 ◽  
Author(s):  
Ronald S. Harwerth ◽  
Joe L. Wheat ◽  
Nalini V. Rangaswamy
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Age Related

scholarly journals Age-related accumulation of phosphorylated mitofusin 2 protein in retinal ganglion cells correlates with glaucoma progression

2017 ◽  
Vol 296 ◽  
pp. 49-61 ◽  
Author(s):  
Mary P. Nivison ◽  
Nolan G. Ericson ◽  
Virginia M. Green ◽  
Jason H. Bielas ◽  
Jean S. Campbell ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Mitofusin 2 ◽  
Glaucoma Progression ◽  
Age Related

scholarly journals Can Variability of Pattern ERG Signal Help to Detect Retinal Ganglion Cells Dysfunction in Glaucomatous Eyes?

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Alberto Mavilio ◽  
Francesca Scrimieri ◽  
Donato Errico
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Second Harmonic ◽  
Pattern Electroretinogram ◽  
Mean Deviation ◽  
Automated Perimetry ◽  
Pattern Erg ◽  
Retinal Ganglion ◽  
Standard Automated Perimetry ◽  
Fiber Layer

Objective. To evaluate variability of steady-state pattern electroretinogram (SS-PERG) signal in normal, suspected, and glaucomatous eyes.Methods. Twenty-one subjects with suspected glaucoma due to disc abnormalities (GS), 37 patients with early glaucoma (EG), and 24 normal control (NC) were tested with spectral-domain optical coherence tomography (SD-OCT), standard automated perimetry (SAP), and SS-PERG. Mean deviation (MD), pattern standard deviation (PSD), retinal nerve fiber layer (RNFL), and ganglionar complex cells (GCC) were evaluated. The SS-PERG was recorded five consecutive times and the amplitude and phase of second harmonic were measured. PERG amplitude and coefficient of variation of phase (CVphase) were recorded, and correlation with structural and functional parameters of disease, by means of one-way ANOVA and Pearson’s correlation, was analysed.Results. PERG amplitude was reduced, as expression of retinal ganglion cells (RGCs) dysfunction, in EG patients and GS subjects compared to NC patients (P<0.0001). CVphase was significantly increased in EG patients and GS subjects, compared to healthy (P<0.0001), and it was also correlated with PSD (P=0.0009), GCC (P=0.028), and RNFL (P=0.0078) only in EG patients.Conclusions. Increased intrasession variability of phase in suspected glaucomatous eyes may be a sign of RGCs dysfunction.

scholarly journals Age Related Response of Neonatal Rat Retinal Ganglion Cells to Reduced TrkB Signaling in vitro and in vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Jamie Beros ◽  
Jennifer Rodger ◽  
Alan R Harvey
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Postnatal Period ◽  
Neonatal Rat ◽  
Retinal Ganglion ◽  
Rat Pups ◽  
Age Related ◽  
Blocking Antibodies

During development of retinofugal pathways there is naturally occurring cell death of at least 50% of retinal ganglion cells (RGCs). In rats, RGC death occurs over a protracted pre- and early postnatal period, the timing linked to the onset of axonal ingrowth into central visual targets. Gene expression studies suggest that developing RGCs switch from local to target-derived neurotrophic support during this innervation phase. Here we investigated, in vitro and in vivo, how RGC birthdate affects the timing of the transition from intra-retinal to target-derived neurotrophin dependence. RGCs were pre-labeled with 5-Bromo-2′-Deoxyuridine (BrdU) at embryonic (E) day 15 or 18. For in vitro studies, RGCs were purified from postnatal day 1 (P1) rat pups and cultured with or without: (i) brain derived neurotrophic factor (BDNF), (ii) blocking antibodies to BDNF and neurotrophin 4/5 (NT-4/5), or (iii) a tropomyosin receptor kinase B fusion protein (TrkB-Fc). RGC viability was quantified 24 and 48 h after plating. By 48 h, the survival of purified βIII-tubulin immunopositive E15 but not E18 RGCs was dependent on addition of BDNF to the culture medium. For E18 RGCs, in the absence of exogenous BDNF, addition of blocking antibodies or TrkB-Fc reduced RGC viability at both 24 and 48 h by 25–40%. While this decrease was not significant due to high variance, importantly, each blocking method also consistently reduced complex process expression in surviving RGCs. In vivo, survival of BrdU and Brn3a co-labeled E15 or E18 RGCs was quantified in rats 24 h after P1 or P5 injection into the eye or contralateral superior colliculus (SC) of BDNF and NT-4/5 antibodies, or serum vehicle. The density of E15 RGCs 24 h after P1 or P5 injection of blocking antibodies was reduced after SC but not intraretinal injection. Antibody injections into either site had little obvious impact on viability of the substantially smaller population of E18 RGCs. In summary, most early postnatal RGC death in the rat involves the elimination of early-born RGCs with their survival primarily dependent upon the availability of target derived BDNF during this time. In contrast, late-born RGC survival may be influenced by additional factors, suggesting an association between RGC birthdate and developmental death mechanisms.

Sign in / Sign up

Export Citation Format

Share Document