Macro- and microglial responses in the fellow eyes contralateral to glaucomatous eyes

Ramírez, Ana I.; Salazar, Juan J.; Hoz, Rosa de; Rojas, Blanca; Gallego, Beatriz; Salobrar‐García, Elena; Valiente‐Soriano, Francisco J.; Triviño, Alberto

doi:10.1016/bs.pbr.2015.05.003

Cited by 28 publications

(25 citation statements)

References 76 publications

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“…[29][30][31] At present we do not know the mechanism responsible for the response in the contralateral fellow eyes, but one possibility is the limited systemic absorption of the injected substances, and, alternatively, that retinal or eye injury results in systemic inflammatory or paracrine-mediated effects that reach the fellow eye. 59 In this latter context, the microglial response may be subtle and not reach statistical significance, as in this study, or may be more intense when the insult is clearly damaging, such as after axotomy 37 or elevation of the intraocular pressure. [59][60][61][62] In summary, this work shows that there are important reactions of the glial cells in the retina to single or repeated IVI of different substances.…”

Section: Effects Of Ivi On the Contralateral Retinamentioning

confidence: 93%

“…59 In this latter context, the microglial response may be subtle and not reach statistical significance, as in this study, or may be more intense when the insult is clearly damaging, such as after axotomy 37 or elevation of the intraocular pressure. [59][60][61][62] In summary, this work shows that there are important reactions of the glial cells in the retina to single or repeated IVI of different substances. All the injected substances cause an important micro-and macroglial response locally at the injection site and widely spread throughout the injected retina that is exacerbated by repeated injections.…”

Section: Effects Of Ivi On the Contralateral Retinamentioning

confidence: 93%

“…For example, topical instillation of saline to one eye resulted in marked upregulation of the mRNA expression levels of fibroblast growth factor 2 (FGF2) in the intact, contralateral fellow retina. 57 More recently, a detailed study of the macro-and microglia has shown that following elevation of the intraocular pressure in one eye, there are marked changes in the contralateral fellow intact eye, [58][59][60][61][62] highlighting the observation that activation of the retinal macro-and microglia in the uninjured eye may result as a consequence of injury to the contralateral fellow eye-thus confirming original observations that unilateral injury to one adult rat optic nerve may cause multiple cellular responses in the contralateral site. 63 In this work we studied the retinal glial response (microglia, astrocytes and Müller cells) of the rodent retina after single or repeated IVI of the substances most used at present in ophthalmology, anti-VEGF and corticosteroids, and their respective vehicles.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Effects Of Ivi On the Contralateral Retinamentioning

confidence: 93%

Section: Effects Of Ivi On the Contralateral Retinamentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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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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“…In mice, RGC death after ON axotomy is already significant at day 3, and stabilizes at day 9, when around 20% of the original RGC population still survives3. Moreover, the effect of the lesion is not confined to the injured retina, since there is a microglial response in the contralateral uninjured retina45. Thus, this model is ideal to study in vivo and relatively quick the fate of axotomized neurons with or without a given treatment3456, i.e.…”

mentioning

confidence: 99%

“…Moreover, the effect of the lesion is not confined to the injured retina, since there is a microglial response in the contralateral uninjured retina45. Thus, this model is ideal to study in vivo and relatively quick the fate of axotomized neurons with or without a given treatment3456, i.e. to test neuroprotective therapies or use genetic approaches to test whether the lack of a given protein is pernicious, protective or innocuous.…”

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confidence: 99%

Involvement of P2X7 receptor in neuronal degeneration triggered by traumatic injury

Nadal-Nicolás

Galindo‐Romero

Valiente‐Soriano

et al. 2016

Sci Rep

Self Cite

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Axonal injury is a common feature of central nervous system insults that culminates with the death of the affected neurons, and an irreversible loss of function. Inflammation is an important component of the neurodegenerative process, where the microglia plays an important role by releasing proinflammatory factors as well as clearing the death neurons by phagocytosis. Here we have identified the purinergic signaling through the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy. We have found that in P2X7 receptor deficient mice there is a delayed loss of retinal ganglion cells and a decrease of phagocytic microglia at early times points after axotomy. In contralateral to the axotomy retinas, P2X7 receptor controlled the numbers of phagocytic microglia, suggesting that extracellular ATP could act as a danger signal activating the P2X7 receptor in mediating the loss of neurons in contralateral retinas. Finally, we show that intravitreal administration of the selective P2X7 receptor antagonist A438079 also delays axotomy-induced retinal ganglion cell death in retinas from wild type mice. Thus, our work demonstrates that P2X7 receptor signaling is involved in neuronal cell death after axonal injury, being P2X7 receptor antagonism a potential therapeutic strategy.

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Pathological Consequences of Reduced Cerebrospinal Fluid Pressure: Experimental Studies

Zhang

et al. 2019

Ocular Fluid Dynamics

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Macro- and microglial responses in the fellow eyes contralateral to glaucomatous eyes

Cited by 28 publications

References 76 publications

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

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

Involvement of P2X7 receptor in neuronal degeneration triggered by traumatic injury

Pathological Consequences of Reduced Cerebrospinal Fluid Pressure: Experimental Studies

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