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EFFECT OF TRIGONELLINE IN A MODEL OF APOPTOSIS IN RAT RETINA

Yıl 2024, Cilt: 10 Sayı: 2, 349 - 365, 31.08.2024

Öz

Purpose: Determine the effectiveness of drop trigonelline and oral trigonelline (TG) as treatments for retinal apoptosis caused by N-methyl D-aspartate (NMDA) and to compare the effectiveness of TG drops with brimonidine tartrate (BT) drops.
Methods: We randomly divided rats into six groups of seven each. We didn’t apply any action to Group1. On the first day of the experiment (FDE), we administered intravitreal phosphate buffered saline (PBS) to Group2, the negative control, without administering any treatment. We administered intravitreal NMDA to Groups 3, 4, 5, and 6 on the FDE. Group3 (the positive control) didn’t receive post-injection treatment. Group4 received oral TG, Group5 received TG drops; and Group6 received BT drops. All rats underwent histopathological and biochemical evaluations.
Results: TUNEL labeling revealed no significant changes between Groups 1 (1.21±0.08) and 2 (1.27±0.11), whereas Group 3 (12.52±2.82) had considerably higher indices (p<0.001). Compared to Group3, drop TG (4.67±1.23) and drop BT (4.26±0.97) significantly reduced apoptosis (p<0.001). MDA levels peaked in Group3 (3.23±0.85), with substantial reductions in all treatment groups (p<0.05). SOD levels decreased considerably in Group3 (14.6±4.01) compared to group 1 (31.51±8.04, p<0.001), while oral TG, drop TG, and drop BT increased significantly (34.73±5.16, 38.46±3.60, 35.98±4.89, p<0.001). In Group3, iNOs protein expression increased by 32%, while the drop TG (~21%, p=0.037) and drop BT (~20%, p=0.04) groups showed substantial declines.
Conclusion: Our study found that the retinal neuroprotective and antioxidant efficacy of TG drops was comparable to that of BT drops.

Kaynakça

  • 1. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–2090.
  • 2. Stein JD, Khawaja AP, Weizer JS. Glaucoma in Adults-Screening, Diagnosis, and Management: A Review. JAMA. 2021;12;325(2):164-174.
  • 3. Levin LA, Crowe ME, Quigley HA, Cordeiro MF, Donoso LA, Liao YJ, et al. Neuroprotection for glaucoma: Requirements for clinical translation. Exp Eye Res. 2017;157:34-37.
  • 4. Joo CK, Choi JS, Ko HW, Park KY, Sohn S, Chun MH, et al. Necrosis and apoptosis after retinal ischemia: Involvement of NMDA- mediated excitotoxicity and p53. Invest Ophthalmol Vis Sci. 1999;40(3):713-720.
  • 5. Shen WC, Huang BQ, Yang J. Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies. Neural Regen Res. 2023;18(1):87-93.
  • 6. Niwa M, Aoki H, Hirata A, Tomita H, Green PG, Hara A. Retinal cell degeneration in animal models. Int J Mol Sci. 2016;15;17(1):110.
  • 7. Panda S, Biswas S, Kar A. Trigonelline isolated from fenugreek seed protects against isoproterenol induced myocardial injury through down-regulation of Hsp27 and αB-crystallin. Nutrition. 2013 Nov-Dec;29(11-12):1395-1403.
  • 8. Zhou J, Chan L, Zhou S. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Curr Med Chem. 2012;19(21):3523-3531.
  • 9. Wheeler LA, Lai R, Woldemussie E. From the lab to the clinic: activation of an a2 agonist pathway is neuroprotective in models of retinal and optic nerve injury. Eur J Ophthalmol. 1999;9:17-21.
  • 10. Kalapesi FB, Coroneo MT, Hill MA. Human ganglion cells express the alpha-2 adrenergic receptor: Relevance to neuroprotection. Br J Ophthalmol. 2005;89(6):758-763.
  • 11. Ozdemir G, Tolun FI, Gul M, Imrek S. Retinal oxidative stress induced by intraocular hypertension in rats may be ameliorated by brimonidine treatment and n-acetyl cysteine supplementation. J Glaucoma. 2009;18(9):662-665.
  • 12. Mirzaie M, Khalili M, Kiasalari Z, Roghani M. Neuroprotective and antiapoptotic potential of trigonelline in a striatal 6-hydroxydopamine rat model of Parkinson’s disease. Neurophysiology. 2016;48(3):176-183.
  • 13. Fahanik-Babaei J, Baluchnejadmojarad T, Nikbakht F, Roghani M. Trigonelline protects hippocampus against intracerebral Aβ(1–40) as a model of Alzheimer’s disease in the rat: insights into underlying mechanisms. Metab Brain Dis. 2019;34(1):191-201.
  • 14. Erisgin Z, Ozer MA, Tosun M, Ozen S, Takir S. The effects of intravitreal H2S application on apoptosis in the retina and cornea in experimental glaucoma model. Int J Exp Pathol. 2019;100(5-6):330-6.
  • 15. Peterson GL. Review of the Folin phenol protein quantitation method of Lowry, Rosebrough, Farr and Randall. Anal Biochem. 1979;100(2):201-220.
  • 16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-8.
  • 17. Harrell C, Fellabaum C, Arsenijević A, Marković B, Djonov V, Volarević V. Therapeutic potential of mesenchymal stem cells and their secretome in the treatment of glaucoma. Stem Cells Int. 2019;2019:7869130.
  • 18. Samelska K, Zaleska-Żmijewska A, Bałan B, Grąbczewski A, Szaflik J, Kubiak A, et al. Immunological and molecular basics of the primary open angle glaucoma pathomechanism. Central Eur J Immunol. 2021;46(1):111-117.
  • 19. Yan J, Yang X, Jiao X, Yang X, Guo M, Chen Y, et al. Integrative transcriptomic and proteomic analysis reveals CD9/ITGA4/PI3K-AKT axis mediates trabecular meshwork cell apoptosis in human glaucoma. J Cell Mol Med. 2019;24(1):814-829.
  • 20. Tasneem Z Khatib, Keith R Martin. Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine. Curr Eye Res. 2020 Mar;45(3):327-338.
  • 21. Li Q, Cheng Y, Zhang S, Sun X, Wu J. Trpv4-induced müller cell gliosis and tnf-α elevation-mediated retinal ganglion cell apoptosis in glaucomatous rats via jak2/stat3/nf-κb pathway. J Neuroinflammation. 2021;18(1). doi: 10.1186/s12974-021-02315-8
  • 22. Kimura A, Namekata K, Guo X, Noro T, Harada C, Harada T. Targeting oxidative stress for treatment of glaucoma and optic neuritis. Oxid Med Cell Longev. 2017;2017:1-8. doi: 10.1155/2017/2817252
  • 23. Wang Y, Huang C, Zhang H, Wu R. Autophagy in glaucoma: crosstalk with apoptosis and its implications. Brain Res Bull. 2015;117:1-9. doi: 10.1016/j.brainresbull.2015.06.001
  • 24. Lossi L. The concept of intrinsic versus extrinsic apoptosis. Biochem J. 2022 Feb 11;479(3):357-384. doi: 10.1042/BCJ20210854
  • 25. Liu Y, Yan H, Chen S, Sabel BA. Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision restoration after rabbit traumatic optic nerve injury. Restor Neurol Neurosci. 2015;33(2):205-20. doi: 10.3233/RNN-159001
  • 26. Ilavenil S, Kim DH, Jeong Y, Arasu MV, Prabhu PN, Srigopalram S, et al. Trigonelline protects the cardiocyte from hydrogen peroxide induced apoptosis in H9c2 cells. Asian Pac J Trop Med. 2015;8(4):263–268.
  • 27. Li Q, Zhang L, Xu Y. Label-free lc–ms/ms proteomics analyses reveal proteomic changes in oxidative stress and the sod antioxidant strategy in tm cells. Clin Proteomics. 2022;19(1). doi: 10.1186/s12014-022-09350-4
  • 28. Inman DM, Lambert WS, Calkins DJ, Horner PJ. Α-lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction. PLoS ONE. 2013;8(6):e65389. doi: 10.1371/journal.pone.0065389
  • 29. Młynarczyk M, Falkowska M, Micun Z, Obuchowska I, Kochanowicz J, Socha K, et al. Diet, oxidative stress, and blood serum nutrients in various types of glaucoma: a systematic review. Nutrients. 2022;14(7):1421. doi: 10.3390/nu14071421
  • 30. Khalili M, Alavi M, Esmaeil-Jamaat E, Baluchnejadmojarad T, Roghani M. Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and antiinflammatory effect. Int Immunopharmacol. 2018;61:355–62. doi: 10.1016/j.intimp.2018.06.019
  • 31. Hu M. Geniposide attenuates oxygen-glucose deprivation/recovery-induced retinal ganglion cell injury via akt/nrf-2 signaling pathway. Curr Med Chem. 2024;31. doi: 10.2174/0109298673272406231212054710
  • 32. Ahn H, Yang J, Kim J, Lee C, Kim T, Jung S. The intraocular pressure-lowering effect of persimmon leaves (diospyros kaki) in a mouse model of glaucoma. Int J Mol Sci. 2019;20(21):5268. doi: 10.3390/ijms20215268
  • 33. Kim H. Scaav2-mediated expression of thioredoxin 2 and c3 transferase prevents retinal ganglion cell death and lowers intraocular pressure in a mouse model of glaucoma. Int J Mol Sci. 2023;24(22):16253. doi: 10.3390/ijms242216253
  • 34. Ishimaru Y, Sumino A, Fujimoto M, Shibagaki F, Yamamuro A, Yoshioka Y, et al. Protective effect of an apelin receptor agonist on retinal ganglion cell death induced by retinal ischemia-reperfusion injury in mice. Proceedings for Annual Meeting of the Japanese Pharmacological Society, WCP2018;2018(0):PO2-1-17. doi: 10.1254/jpssuppl.wcp2018.0_po2-1-17
  • 35. Li Q, Fang W, Hu F, Zhou X, Cheng Y, Jiang C. A high salt diet aggravates retinal ischaemia/reperfusion injury. Exp Eye Res. 2019. doi: 10.1016/j.exer.2019.107784
  • 36. Schnichels S, Schultheiss M, Klemm P, Blak M, Herrmann T, Melchinger M, et al. Cyclosporine A protects retinal explants against hypoxia. Int J Mol Sci. 2021;22(19):10196. doi: 10.3390/ijms221910196
  • 37. Wang F, Dang Y, Wang J, Zhou T, Zhu Y. Gypenosides attenuate lipopolysaccharide-induced optic neuritis in rats. Acta Histochem. 2018 May;120(4):340-346. doi: 10.1016/j.acthis.2018.03.003.
  • 38. Nadal-Nicolás FM, Jiménez-López M, Sobrado-Calvo P, Nieto-López L, Cánovas-Martinez I, Salinas-Navarro M, et al. Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naïve and optic nerve-injured retinas. Invest Ophthalmol Vis Sci. 2009;50(8):3860-8. doi: 10.1167/iovs.08-3267
  • 39. Takahashi N, Matsunaga N, Natsume T, Kitazawa C, Itani Y, Hama A, et al. A longitudinal comparison in cynomolgus macaques of the effect of brimonidine on optic nerve neuropathy using diffusion tensor imaging magnetic resonance imaging and spectral domain optical coherence tomography. Heliyon. 2021;7(4):e06701. doi: 10.1016/j.heliyon.2021.e06701
  • 40. Bagli E, Kitsos G. Neuroprotective agents in glaucoma. The Mystery of Glaucoma. 2011. doi: 10.5772/19067

RAT RETİNASINDAKİ APOPİTOZİS MODELİNDE TRİGONELLİNE ETKİNLİĞİ

Yıl 2024, Cilt: 10 Sayı: 2, 349 - 365, 31.08.2024

Öz

Amaç: N-metil D-aspartat (NMDA) ile indüklenmiş retinal apopitozis modelinde damla trigoneline ve oral trigonelinenin (TG) etkinliğini belirlemek ve TG etkinliğini brimonidin tartarat (BT) ile karşılaştırmak.
Yöntemler: Ratlar, her birinde yedi rat olacak şekilde rastgele altı gruba ayrıldı. Grup1'e herhangi bir işlem veya tedavi uygulanmadı. Deneyin ilk gününde (DİG) Grup 2'ye (negatif kontrol) intravitreal fosfat tamponlu salin (PBS) uygulandı ve sonrasında herhangi bir tedavi verilmedi. DİG'de Grup 3, 4, 5 ve 6'ya intravitreal NMDA uygulandı. Grup3’e (pozitif kontrol), enjeksiyon sonrası tedavi uygulanmadı. Grup4'e oral TG, Grup5'e damla TG ve Grup6’ya damla BT tedavisi verildi. Tüm rat gözlerinde histopatolojik ve biyokimyasal değerlendirmeler yapıldı.
Bulgular: TUNEL boyamasında, Grup 1 (1,21±0,08) ve 2 (1,27±0,11) arasında anlamlı bir fark olmadığı görüldü. Grup3'ün (12,52±2,82), Grup1’e göre yüksek düzeyde apopitotik indekse sahip olduğu izlendi (p<0,001). Grup3 ile karşılaştırıldığında damla TG (4,67±1,23) ve damla BT (4,26±0,97) gruplarında apopitozis anlamlı derecede azdı (p<0,001). MDA düzeyleri Grup 3'te yüksek izlenirken (3,23±0,85), tüm tedavi gruplarında önemli azalmalar görüldü (p<0,05). SOD düzeyleri grup 3'te (14,6±4,01) grup 1'e (31,51±8,04, p<0,001) göre anlamlı derecede azken, oral TG, damla TG ve damla BT gruplarında anlamlı düzeyde yüksek izlendi (34,73±5,16, 38,46±3,60, 35,98±4,89) , p<0.001). Grup3'te iNOs protein ekspresyonu %32 düzeylerindeyken, damla TG (~%21, p=0,037) ve damla BT (~%20, p=0,04) gruplarında ciddi azalmalar görüldü.
Sonuç: Çalışmamız, damla TG’nin retinal nöroprotektif ve antioksidan etkinliğinin, damla BT ile benzer düzeyde olduğunu tespit etmiştir.

Kaynakça

  • 1. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–2090.
  • 2. Stein JD, Khawaja AP, Weizer JS. Glaucoma in Adults-Screening, Diagnosis, and Management: A Review. JAMA. 2021;12;325(2):164-174.
  • 3. Levin LA, Crowe ME, Quigley HA, Cordeiro MF, Donoso LA, Liao YJ, et al. Neuroprotection for glaucoma: Requirements for clinical translation. Exp Eye Res. 2017;157:34-37.
  • 4. Joo CK, Choi JS, Ko HW, Park KY, Sohn S, Chun MH, et al. Necrosis and apoptosis after retinal ischemia: Involvement of NMDA- mediated excitotoxicity and p53. Invest Ophthalmol Vis Sci. 1999;40(3):713-720.
  • 5. Shen WC, Huang BQ, Yang J. Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies. Neural Regen Res. 2023;18(1):87-93.
  • 6. Niwa M, Aoki H, Hirata A, Tomita H, Green PG, Hara A. Retinal cell degeneration in animal models. Int J Mol Sci. 2016;15;17(1):110.
  • 7. Panda S, Biswas S, Kar A. Trigonelline isolated from fenugreek seed protects against isoproterenol induced myocardial injury through down-regulation of Hsp27 and αB-crystallin. Nutrition. 2013 Nov-Dec;29(11-12):1395-1403.
  • 8. Zhou J, Chan L, Zhou S. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Curr Med Chem. 2012;19(21):3523-3531.
  • 9. Wheeler LA, Lai R, Woldemussie E. From the lab to the clinic: activation of an a2 agonist pathway is neuroprotective in models of retinal and optic nerve injury. Eur J Ophthalmol. 1999;9:17-21.
  • 10. Kalapesi FB, Coroneo MT, Hill MA. Human ganglion cells express the alpha-2 adrenergic receptor: Relevance to neuroprotection. Br J Ophthalmol. 2005;89(6):758-763.
  • 11. Ozdemir G, Tolun FI, Gul M, Imrek S. Retinal oxidative stress induced by intraocular hypertension in rats may be ameliorated by brimonidine treatment and n-acetyl cysteine supplementation. J Glaucoma. 2009;18(9):662-665.
  • 12. Mirzaie M, Khalili M, Kiasalari Z, Roghani M. Neuroprotective and antiapoptotic potential of trigonelline in a striatal 6-hydroxydopamine rat model of Parkinson’s disease. Neurophysiology. 2016;48(3):176-183.
  • 13. Fahanik-Babaei J, Baluchnejadmojarad T, Nikbakht F, Roghani M. Trigonelline protects hippocampus against intracerebral Aβ(1–40) as a model of Alzheimer’s disease in the rat: insights into underlying mechanisms. Metab Brain Dis. 2019;34(1):191-201.
  • 14. Erisgin Z, Ozer MA, Tosun M, Ozen S, Takir S. The effects of intravitreal H2S application on apoptosis in the retina and cornea in experimental glaucoma model. Int J Exp Pathol. 2019;100(5-6):330-6.
  • 15. Peterson GL. Review of the Folin phenol protein quantitation method of Lowry, Rosebrough, Farr and Randall. Anal Biochem. 1979;100(2):201-220.
  • 16. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-8.
  • 17. Harrell C, Fellabaum C, Arsenijević A, Marković B, Djonov V, Volarević V. Therapeutic potential of mesenchymal stem cells and their secretome in the treatment of glaucoma. Stem Cells Int. 2019;2019:7869130.
  • 18. Samelska K, Zaleska-Żmijewska A, Bałan B, Grąbczewski A, Szaflik J, Kubiak A, et al. Immunological and molecular basics of the primary open angle glaucoma pathomechanism. Central Eur J Immunol. 2021;46(1):111-117.
  • 19. Yan J, Yang X, Jiao X, Yang X, Guo M, Chen Y, et al. Integrative transcriptomic and proteomic analysis reveals CD9/ITGA4/PI3K-AKT axis mediates trabecular meshwork cell apoptosis in human glaucoma. J Cell Mol Med. 2019;24(1):814-829.
  • 20. Tasneem Z Khatib, Keith R Martin. Neuroprotection in Glaucoma: Towards Clinical Trials and Precision Medicine. Curr Eye Res. 2020 Mar;45(3):327-338.
  • 21. Li Q, Cheng Y, Zhang S, Sun X, Wu J. Trpv4-induced müller cell gliosis and tnf-α elevation-mediated retinal ganglion cell apoptosis in glaucomatous rats via jak2/stat3/nf-κb pathway. J Neuroinflammation. 2021;18(1). doi: 10.1186/s12974-021-02315-8
  • 22. Kimura A, Namekata K, Guo X, Noro T, Harada C, Harada T. Targeting oxidative stress for treatment of glaucoma and optic neuritis. Oxid Med Cell Longev. 2017;2017:1-8. doi: 10.1155/2017/2817252
  • 23. Wang Y, Huang C, Zhang H, Wu R. Autophagy in glaucoma: crosstalk with apoptosis and its implications. Brain Res Bull. 2015;117:1-9. doi: 10.1016/j.brainresbull.2015.06.001
  • 24. Lossi L. The concept of intrinsic versus extrinsic apoptosis. Biochem J. 2022 Feb 11;479(3):357-384. doi: 10.1042/BCJ20210854
  • 25. Liu Y, Yan H, Chen S, Sabel BA. Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision restoration after rabbit traumatic optic nerve injury. Restor Neurol Neurosci. 2015;33(2):205-20. doi: 10.3233/RNN-159001
  • 26. Ilavenil S, Kim DH, Jeong Y, Arasu MV, Prabhu PN, Srigopalram S, et al. Trigonelline protects the cardiocyte from hydrogen peroxide induced apoptosis in H9c2 cells. Asian Pac J Trop Med. 2015;8(4):263–268.
  • 27. Li Q, Zhang L, Xu Y. Label-free lc–ms/ms proteomics analyses reveal proteomic changes in oxidative stress and the sod antioxidant strategy in tm cells. Clin Proteomics. 2022;19(1). doi: 10.1186/s12014-022-09350-4
  • 28. Inman DM, Lambert WS, Calkins DJ, Horner PJ. Α-lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction. PLoS ONE. 2013;8(6):e65389. doi: 10.1371/journal.pone.0065389
  • 29. Młynarczyk M, Falkowska M, Micun Z, Obuchowska I, Kochanowicz J, Socha K, et al. Diet, oxidative stress, and blood serum nutrients in various types of glaucoma: a systematic review. Nutrients. 2022;14(7):1421. doi: 10.3390/nu14071421
  • 30. Khalili M, Alavi M, Esmaeil-Jamaat E, Baluchnejadmojarad T, Roghani M. Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and antiinflammatory effect. Int Immunopharmacol. 2018;61:355–62. doi: 10.1016/j.intimp.2018.06.019
  • 31. Hu M. Geniposide attenuates oxygen-glucose deprivation/recovery-induced retinal ganglion cell injury via akt/nrf-2 signaling pathway. Curr Med Chem. 2024;31. doi: 10.2174/0109298673272406231212054710
  • 32. Ahn H, Yang J, Kim J, Lee C, Kim T, Jung S. The intraocular pressure-lowering effect of persimmon leaves (diospyros kaki) in a mouse model of glaucoma. Int J Mol Sci. 2019;20(21):5268. doi: 10.3390/ijms20215268
  • 33. Kim H. Scaav2-mediated expression of thioredoxin 2 and c3 transferase prevents retinal ganglion cell death and lowers intraocular pressure in a mouse model of glaucoma. Int J Mol Sci. 2023;24(22):16253. doi: 10.3390/ijms242216253
  • 34. Ishimaru Y, Sumino A, Fujimoto M, Shibagaki F, Yamamuro A, Yoshioka Y, et al. Protective effect of an apelin receptor agonist on retinal ganglion cell death induced by retinal ischemia-reperfusion injury in mice. Proceedings for Annual Meeting of the Japanese Pharmacological Society, WCP2018;2018(0):PO2-1-17. doi: 10.1254/jpssuppl.wcp2018.0_po2-1-17
  • 35. Li Q, Fang W, Hu F, Zhou X, Cheng Y, Jiang C. A high salt diet aggravates retinal ischaemia/reperfusion injury. Exp Eye Res. 2019. doi: 10.1016/j.exer.2019.107784
  • 36. Schnichels S, Schultheiss M, Klemm P, Blak M, Herrmann T, Melchinger M, et al. Cyclosporine A protects retinal explants against hypoxia. Int J Mol Sci. 2021;22(19):10196. doi: 10.3390/ijms221910196
  • 37. Wang F, Dang Y, Wang J, Zhou T, Zhu Y. Gypenosides attenuate lipopolysaccharide-induced optic neuritis in rats. Acta Histochem. 2018 May;120(4):340-346. doi: 10.1016/j.acthis.2018.03.003.
  • 38. Nadal-Nicolás FM, Jiménez-López M, Sobrado-Calvo P, Nieto-López L, Cánovas-Martinez I, Salinas-Navarro M, et al. Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naïve and optic nerve-injured retinas. Invest Ophthalmol Vis Sci. 2009;50(8):3860-8. doi: 10.1167/iovs.08-3267
  • 39. Takahashi N, Matsunaga N, Natsume T, Kitazawa C, Itani Y, Hama A, et al. A longitudinal comparison in cynomolgus macaques of the effect of brimonidine on optic nerve neuropathy using diffusion tensor imaging magnetic resonance imaging and spectral domain optical coherence tomography. Heliyon. 2021;7(4):e06701. doi: 10.1016/j.heliyon.2021.e06701
  • 40. Bagli E, Kitsos G. Neuroprotective agents in glaucoma. The Mystery of Glaucoma. 2011. doi: 10.5772/19067
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Görme Bilimi, Göz Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Sevinç Arzu Postacı

Ali Dal 0000-0002-0748-6416

Ülkü Çeliker

Nevin İlhan

Ferda Dağlı

Erken Görünüm Tarihi 3 Eylül 2024
Yayımlanma Tarihi 31 Ağustos 2024
Gönderilme Tarihi 17 Temmuz 2024
Kabul Tarihi 31 Ağustos 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 10 Sayı: 2

Kaynak Göster

APA Postacı, S. A., Dal, A., Çeliker, Ü., İlhan, N., vd. (2024). EFFECT OF TRIGONELLINE IN A MODEL OF APOPTOSIS IN RAT RETINA. International Anatolia Academic Online Journal Health Sciences, 10(2), 349-365.

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