Retinal neurodegeneration in experimental glaucoma

Vidal‐Sanz, Manuel; Valiente‐Soriano, Francisco J.; Ortín-Martínez, Arturo; Nadal-Nicolás, Francisco M.; Jiménez-López, Manuel; Salinas‐Navarro, Manuel; Alarcón-Martínez, Luis; García‐Ayuso, Diego; Avilés‐Trigueros, Marcelino; Agudo‐Barriuso, Marta; Villegas‐Pérez, María Paz

doi:10.1016/bs.pbr.2015.04.008

Cited by 67 publications

(60 citation statements)

References 163 publications

(285 reference statements)

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“…With these quantitative data, isodensity maps of Brn3a + RGCs were constructed using a graphing software ( sigmaplot © r ) as reported (Vidal‐Sanz et al. 2012, 2015a,b). For quantitative analysis of the Iba‐1 + microglia in the ganglion cell layer, 12 rectangular areas (0.36 × 0.24 mm) at a magnification of ×100 were taken from concentric zones of each retina, three per quadrant at equidistant distances from the optic disk.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA regulation in an animal model of acute ocular hypertension

Wang

Valiente‐Soriano

Nadal-Nicolás

et al. 2016

Acta Ophthalmologica

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PurposeTo analyse miRNA regulation in a rat model of acute ocular hypertension (AOH).MethodsAcute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT‐PCR and Western blotting.ResultsAnatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT‐PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen‐activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor‐alpha (TNF‐α) and iNOS proteins were significantly upregulated in the AOH retinas.ConclusionsAcute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia‐mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions.

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Section: Methodsmentioning

confidence: 99%

MicroRNA regulation in an animal model of acute ocular hypertension

Wang

Valiente‐Soriano

Nadal-Nicolás

et al. 2016

Acta Ophthalmologica

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“…We have recently described that in the rat Brn3a is expressed by approximately 96% of the RGCs while the remaining 4% which do not express Brn3a is composed of approximately one half of the ipsilaterally projecting RGCs (1.3%) and the melanopsin expressing RGCs (m + RGCs) (2.6%) (Nadal-Nicolás et al, 2012, 2014; Galindo-Romero et al, 2013a; Valiente-Soriano et al, 2014). The differential expression of these two proteins, Brn3a and melanopsin, by the two functional types of RGCs makes double immunodetection a great tool to study in the same retinas the fate of these two distinct RGC populations upon injury and/or neuroprotection (Vidal-Sanz et al, 2015a,b; Agudo-Barriuso et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

“…There are several ways to raise artificially the IOP in rodents (for review see, Morrison et al, 2011; Vidal-Sanz et al, 2012, 2015a). Here, we will focus on a chronic and an acute model of ocular hypertension; the laser photocoagulation of limbar and perilimbar tissues and the anterior chamber cannulation.…”

Section: Introductionmentioning

confidence: 99%

Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension

et al. 2017

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Glaucoma, one of the leading causes of blindness worldwide, affects primarily retinal ganglion cells (RGCs) and their axons. The pathophysiology of glaucoma is not fully understood, but it is currently believed that damage to RGC axons at the optic nerve head plays a major role. Rodent models to study glaucoma include those that mimic either ocular hypertension or optic nerve injury. Here we review the anatomical loss of the general population of RGCs (that express Brn3a; Brn3a+RGCs) and of the intrinsically photosensitive RGCs (that express melanopsin; m+RGCs) after chronic (LP-OHT) or acute (A-OHT) ocular hypertension and after complete intraorbital optic nerve transection (ONT) or crush (ONC). Our studies show that all of these insults trigger RGC death. Compared to Brn3a+RGCs, m+RGCs are more resilient to ONT, ONC, and A-OHT but not to LP-OHT. There are differences in the course of RGC loss both between these RGC types and among injuries. An important difference between the damage caused by ocular hypertension or optic nerve injury appears in the outer retina. Both axotomy and LP-OHT induce selective loss of RGCs but LP-OHT also induces a protracted loss of cone photoreceptors. This review outlines our current understanding of the anatomical changes occurring in rodent models of glaucoma and discusses the advantages of each one and their translational value.

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“…The 154 frames/retina were combined automatically into a single tiled high-resolution photomontage using IPP for Windows. 50,71 Magnifications of some retinas were also taken with a confocal microscope (Spectral confocal & multiphoton system Leica TCS SP2; Leica, Jena, Germany). The same settings were always used to acquire GFAP, Iba-1, and vimentin signals.…”

Section: Image Acquisition and Analysismentioning

confidence: 99%

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

Pierdomenico

García‐Ayuso

Jiménez-López

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Di Pierdomenico J, García-Ayuso D, Jiménez-López M, AgudoBarriuso M, Vidal-Sanz M, VillegasPérez MP. Different ipsi-and contralateral glial responses to anti-VEGF and triamcinolone intravitreal injections in rats. Invest Ophthalmol Vis Sci. 2016;57:3533-3544. DOI:10.1167/iovs.16-19618 PURPOSE. To investigate the glial response of the rat retina to single or repeated intravitreal injections (IVI).METHODS. Albino Sprague-Dawley rats received one or three (one every 7 days) IVI of anti-rat VEGF (5 lL; 0.015 lg/lL), triamcinolone (2.5 or 5 lL; 40 lg/lL; Trigón Depot), bevacizumab (5 lL; 25 lg/lL; Avastin), or their vehicles (PBS and balanced salt solution) and were processed 7 days after the last injection. Retinas were dissected as whole mounts and incubated with antibodies against: Iba1 (Ionized Calcium-Binding Adapter Molecule 1) to label retinal microglia, GFAP (Glial Fibrillary Acidic Protein) to label macroglial cells, and vimentin to label Müller cells. The retinas were examined with fluorescence and confocal microscopy, and the numbers of microglial cells in the inner retinal layers were quantified using a semiautomatic method.RESULTS. All the injected substances caused an important micro-and macroglial response locally at the injection site and all throughout the injected retina that was exacerbated by repeated injections. The microglial response was also observed but was milder in the contralateral noninjected eyes. The IVI of the humanized antibody bevacizumab caused a very strong microglial reaction in the ipsilateral retina. Two types of macroglial response were observed: astrocyte hypertrophy and Müller end-foot hypertrophy. While astrocyte hypertrophy was widespread throughout the injected retina, Müller end-foot hypertrophy was localized and more extensive with triamcinolone use or after repeated injections. CONCLUSIONS.Intravitreal injections cause micro-and macroglial responses that vary depending on the injected agent but increase with repeated injections. This inflammatory glial response may influence the effects of the injected substances on the retina.

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Retinal neurodegeneration in experimental glaucoma

Cited by 67 publications

References 163 publications

MicroRNA regulation in an animal model of acute ocular hypertension

MicroRNA regulation in an animal model of acute ocular hypertension

Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

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