Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration DOI Creative Commons

Ping‐Wu Zhang,

Zi-He Wan,

Weifeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Background The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these limited at best. Genetic other preclinical evidence suggest a relationship between inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival function in mouse model of light damage (LD)-induced Methods LD was induced exposing mice to 4000 lux 2–4 hrs. IBU (100 or 200 mg/kg) vehicle administered daily intraperitoneal injection. Retinal structure were evaluated spectral-domain optical coherence tomography (SD-OCT) electroretinography (ERG). cell death genes analyzed 24 72 hours (hrs) after the Mouse Pan-Cell Death Pathway PCR Array (88 genes). cellular location protein expression key necroptosis gene assessed immunohistochemistry. Results outer nuclear layer (ONL) thickness vehicle-injected animals 8.7 ± 0.6% retinas without (p < 0.0001). In 200mg/kg treated mice, central ONL 74.9 7.7% untreated 0.001). A-wave b-wave ERG amplitudes significantly preserved IBU-treated animals. inhibited Twenty-four hrs LD, mRNA inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), C-C motif chemokine ligand 2 (Ccl2) increased 10, 17 533-fold, respectively; animals, levels inflammatory factors not different no-LD controls. Expression genes, including Ripk3 Mlkl, upregulated vehicle-treated but dramatically reduced near no mice. Microglia activation MLKL upregulation observed primarily photoreceptors 12 as microglia migration plexiform (OPL) retinas. Conclusions Systemic administration partially protected light-induced photochemical both inflammation pathways. Our results that NSAIDs may provide promising therapeutic approach treatment human diseases.

Language: Английский

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration DOI Creative Commons

Ping‐Wu Zhang,

Zi-He Wan,

Weifeng Li

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 28, 2025

Abstract Background The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these limited at best. Genetic other preclinical evidence suggest a relationship between inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival function in mouse model of light damage (LD)-induced Methods LD was induced exposing mice to 4000 lx 2–4 hours (h). IBU (100 or 200 mg/kg) vehicle administered daily intraperitoneal injection. Retinal structure were evaluated spectral-domain optical coherence tomography (SD-OCT) electroretinography (ERG). Cell death genes analyzed 24 72 h after using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). cellular location protein expression key necroptosis assessed immunohistochemistry. Results outer nuclear layer (ONL) thickness vehicle-injected animals 8.7 ± 0.6% retinas without ( p < 0.0001). In mg/kg treated mice, central ONL 74.9 7.7% untreated 0.001). A-wave b-wave ERG amplitudes significantly preserved IBU-treated animals. inhibited Twenty-four hour LD, mRNA inflammatory-factors tumor necrosis factor Tnf ), interleukin-1 beta Il1B C-C motif chemokine ligand 2 Ccl2 ) increased 10-, 17-, 533-fold, respectively; animals, levels inflammatory factors not different no-LD controls. Expression genes, including Ripk3 Mlkl , upregulated vehicle-treated but dramatically reduced near no mice. Microglia activation MLKL upregulation observed primarily photoreceptors 12 as microglia migration plexiform (OPL) retinas. Conclusions Systemic administration partially protected light-induced photochemical both inflammation cell pathways. Our results that NSAIDs may provide promising therapeutic approach treatment human diseases.

Language: Английский

Citations

0
Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration DOI Creative Commons

Ping‐Wu Zhang,

Zi-He Wan,

Weifeng Li

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Background The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these limited at best. Genetic other preclinical evidence suggest a relationship between inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival function in mouse model of light damage (LD)-induced Methods LD was induced exposing mice to 4000 lux 2–4 hrs. IBU (100 or 200 mg/kg) vehicle administered daily intraperitoneal injection. Retinal structure were evaluated spectral-domain optical coherence tomography (SD-OCT) electroretinography (ERG). cell death genes analyzed 24 72 hours (hrs) after the Mouse Pan-Cell Death Pathway PCR Array (88 genes). cellular location protein expression key necroptosis gene assessed immunohistochemistry. Results outer nuclear layer (ONL) thickness vehicle-injected animals 8.7 ± 0.6% retinas without (p < 0.0001). In 200mg/kg treated mice, central ONL 74.9 7.7% untreated 0.001). A-wave b-wave ERG amplitudes significantly preserved IBU-treated animals. inhibited Twenty-four hrs LD, mRNA inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1b), C-C motif chemokine ligand 2 (Ccl2) increased 10, 17 533-fold, respectively; animals, levels inflammatory factors not different no-LD controls. Expression genes, including Ripk3 Mlkl, upregulated vehicle-treated but dramatically reduced near no mice. Microglia activation MLKL upregulation observed primarily photoreceptors 12 as microglia migration plexiform (OPL) retinas. Conclusions Systemic administration partially protected light-induced photochemical both inflammation pathways. Our results that NSAIDs may provide promising therapeutic approach treatment human diseases.

Language: Английский

Citations

0