Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma

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Fernández Arrabal, José A. and Salazar Corral, Juan José and Hoz Montañana, María Rosa de and Marco López, Eva María and Martín Sánchez, Beatriz and Flores Salguero, Elena and García Martín, Elena Salobrar and López Cuenca, Inés and Barrios Sabador, Vicente and Avilés Trigueros, Marcelino and Valiente Soriano, Francisco Javier and Miralles de Imperial-Ollero, Juan A. and Vidal Sanz, Manuel and Triviño Casado, Alberto and Ramirez Sebastian, Jose Manuel and López Gallardo, Meritxell and Ramírez Sebastián, Ana Isabel (2021) Retinal Molecular Changes Are Associated with Neuroinflammation and Loss of RGCs in an Experimental Model of Glaucoma. International Journal of Molecular Sciences, 22 (4). art. 2066-29 p.. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms22042066




Abstract

Signaling mediated by cytokines and chemokines is involved in glaucoma-associated neuroinflammation and in the damage of retinal ganglion cells (RGCs). Using multiplexed immunoassay and immunohistochemical techniques in a glaucoma mouse model at different time points after ocular hypertension (OHT), we analyzed (i) the expression of pro-inflammatory cytokines, anti-inflammatory cytokines, BDNF, VEGF, and fractalkine; and (ii) the number of Brn3a+ RGCs. In OHT eyes, there was an upregulation of (i) IFN-γ at days 3, 5, and 15; (ii) IL-4 at days 1, 3, 5, and 7 and IL-10 at days 3 and 5 (coinciding with downregulation of IL1-β at days 1, 5, and 7); (iii) IL-6 at days 1, 3, and 5; (iv) fractalkine and VEGF at day 1; and (v) BDNF at days 1, 3, 7, and 15. In contralateral eyes, there were (i) an upregulation of IL-1β at days 1 and 3 and a downregulation at day 7, coinciding with the downregulation of IL4 at days 3 and 5 and the upregulation at day 7; (ii) an upregulation of IL-6 at days 1, 5, and 7 and a downregulation at 15 days; (iii) an upregulation of IL-10 at days 3 and 7; and (iv) an upregulation of IL-17 at day 15. In OHT eyes, there was a reduction in the Brn3a+ RGCs number at days 3, 5, 7, and 15. OHT changes cytokine levels in both OHT and contralateral eyes at different time points after OHT induction, confirming the immune system involvement in glaucomatous neurodegeneration.


Item Type:Article
Additional Information:

Received: 26 January 2021 / Revised: 14 February 2021 / Accepted: 17 February 2021 / Published: 19 February 2021.
Este artículo pertenece al Nº especial "Retina Degeneration, Neuroprotection and Repair".

Uncontrolled Keywords:Cytokines; BDNF; VEGF; Fractalkine; Glaucoma; Ocular hypertension; Microglia; Retinal ganglion cells (RGCs); Iba-1; Brn3a
Subjects:Medical sciences > Medicine > Neurosciences
Medical sciences > Medicine > Ophtalmology
Medical sciences > Biology > Cytology
ID Code:64340
Deposited On:10 Mar 2021 08:28
Last Modified:01 Jun 2021 14:31

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