Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms22042066
Keywords
cytokines; BDNF; VEGF; fractalkine; glaucoma; ocular hypertension; microglia; retinal ganglion cells (RGCs); Iba-1; Brn3a
Funding
- Ophthalmological Network OFTARED of the Institute of Health of Carlos III of the Spanish Ministry of Economy [RD16/0008/0005, RD16/0008/0026]
- PN I+D+i 2008-2011
- ISCIII-Subdireccion General de Redes y Centros de Investigacion Cooperativa
- European programme FEDER
- Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional Una Manera de Hacer Europa [PID2019-106498GB-I00, RED2018-102499-T]
- Spanish Ministry of Science, Innovation [CT42/18-CT43/18]
- Fundacion Seneca, Agencia de Ciencia y Tecnologia Region de Murcia [19881/GERM/15]
- Santander-Complutense University of Madrid Research Projects [PR75/18-21560, FPU17/01023]
- Complutense University of Madrid
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Studies have shown that glaucoma leads to changes in cytokine levels after ocular hypertension, confirming the involvement of the immune system in glaucomatous neurodegeneration.
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-gamma 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-beta 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-1 beta 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.
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