Turkiye Klinikleri Journal of Ophthalmology

.: ORIGINAL RESEARCH
Ambliyopi Modelinde, Rolipramin Vizüel Kortikal Plastisite Üzerine Etkisi: Deneysel Hayvan Çalışması
The Effect of Rolipram on Visual Cortical Plasticity in Amblyopia Model: Experimental Animal Study
Esra EMREa , Büşra KATREb , Özgül ALTINTAŞc, Züleyha ŞIK SARMANd , Hüsnü EFENDİe , Başak ÖZKANf , Dilek AKAKINg , Özlem Tuğçe ÇİLİNGİRg , İlkay ÖZDEMİRh , Seyhun SOLAKOĞLUh
aClinic of Ophthalmology, Fatih State Hospital, Trabzon, Türkiye
bClinic of Ophthalmology, Kocaeli State Hospital, Kocaeli, Türkiye
cDepartment of Ophthalmology, Acıbadem Ali Aydınlar University, İstanbul, Türkiye
dClinic of Ophthalmology, Büyükçekmece Mimar Sinan State Hospital, İstanbul, Türkiye
eDepartment of Neurology, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye
fDepartment of Ophthalmology, University of Health Sciences Süreyyapaşa Chest Disease and Thoracic Surgery Training and Research Hospital, İstanbul, Türkiye
gDeparment of Histology and Embryology, Marmara University Faculty of Medicine, İstanbul, Türkiye
hDeparment of Histology and Embryology, İstanbul University Faculty of Medicine İstanbul, İstanbul, Turkey.
Turkiye Klinikleri J Ophthalmol. 2023;32(3):144-52
doi: 10.5336/ophthal.2022-93575
Article Language: TR
Full Text
ÖZET
Amaç: Ratlarda, deneysel monooküler deprivasyon ambliyopisi modelinde rolipramın, vizüel kortikal plastisite üzerindeki etkisinin elektrofizyolojik ve elektron mikroskobik olarak incelenmesidir. Gereç ve Yöntemler: Yirmi dört Wistar albino cinsi rat, her grupta 4 rat olacak şekilde rastgele 6 gruba ayrıldı. Kontrol grubu dışındaki ratlar dışında tüm ratların sağ göz kapakları 21-45. günleri arası sütüre edilerek monooküler deprivasyon modeli oluşturuldu. Kırk altıncı günde tüm ratlara 10 gün boyunca rolipram veya rolipramı çözmek için kullandığımız sıvı uygulandı. Sinaptik kavşaktaki ultrastrüktürel modifikasyonlar ve görsel uyarılmış potansiyellerdeki (VEP) değişiklikler analiz edildi. Bulgular: Deprivasyon ambliyopisi modelinde VEP?te P2 latansının uzadığı, amplütüdün azaldığı ve rolipram ile tedavi sonrası ise latansın kısaldığı ve amplitüdün arttığı ve kontrol grubuna yaklaştığı görüldü. Deprivasyon ambliyopisi modelinde piramidal nöronlardaki sinapsların ultrastrüktüral yapısının bozulduğu, sinaptik yarığın genişlediği, sinaptik aktif zonun uzunluğunun kısaldığı, postsinaptik dansite kalınlığının azaldığı ve rolipram ile tedavi sonrası ise bu değerlerin kontrol grubuna yaklaştığı görüldü. Sonuç: Bu çalışma, rolipramın ratlardaki ambliyopi modelinde, vizüel kortekste yapısal ve fonksiyonel iyileşmeyi sağladığını göstermektedir. Rolipram, ambliyopi tedavisinde umut vadetmektedir ve ileri araştırmalara gerek vardır.

Anahtar Kelimeler: Ambliyopi; fosfodiesteraz inhibitör; nöral plastisite; uyandırılmış potansiyeller, görsel
ABSTRACT
Objective: Electrophysiological and electron microscopic investigation of the effect of rolipram on visual cortical plasticity in a monocular deprived rat model. Material and Methods: Twenty-four female Wistar albino rats were randomly assigned into 6 groups, 4 rats in each. The right eyelids of all rats except the control group were sutured to induce amblyopia. We subjected rats at postnatal day 21 to a monocular deprivation (MD) model until postnatal day 45. Then, the deprived eyes of the MD model rats were reopened? cümlesi çıkarılarak ?On day 46, the deprived eyes of the rats were opened.On day 46, the deprived eyes of the rats were opened. Rats were treated with rolipram or vehicle for 10 days. The ultrastructural modifications in the synaptic junction and the changes to the visual evoked potentials (VEP) were analyzed. Results: In flash VEP, the P2 latency was prolonged and the P2 amplitude was reduced in monocularly deprived rats. With rolipram treatment, the P2 latency became shorter and the amplitude increased. In the monocularly deprived rats, the ultrastructural analysis showed that the synapses in the pyramidal neurons were impaired, the synaptic clefts were expanded, the synaptic active zones were shorter, and the thicknesses of the postsynaptic density were decreased. However, rolipram treatment improved all of the structural indices in the MD rats. Conclusion: This study shows that rolipram provides structural and functional improvement in visual cortex in amblyopia model in rats. Rolipram shows promise in the treatment of amblyopia and more research is needed.

Keywords: Amblyopia; phosphodiesterase inhibitor; neuronal plasticity; evoked potentials, visual
REFERENCES:
  1. Sansevero G, Baroncelli L, Scali M, Sale A. Intranasal BDNF administration promotes visual function recovery in adult amblyopic rats. Neuropharmacology. 2019;145(Pt A):114-22. [Crossref]  [PubMed] 
  2. Li Y, Wang L, Zhang X, Huang M, Li S, Wang X, et al. Inhibition of Cdk5 rejuvenates inhibitory circuits and restores experience-dependent plasticity in adult visual cortex. Neuropharmacology. 2018;128:207-20. [Crossref]  [PubMed] 
  3. McGee AW, Yang Y, Fischer QS, Daw NW, Strittmatter SM. Experience-driven plasticity of visual cortex limited by myelin and Nogo receptor. Science. 2005;309(5744):2222-6. [Crossref]  [PubMed]  [PMC] 
  4. Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005;6(11):877-88. [Crossref]  [PubMed] 
  5. Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science. 2002;298(5596):1248-51. [Crossref]  [PubMed] 
  6. McCoy PA, Huang HS, Philpot BD. Advances in understanding visual cortex plasticity. Curr Opin Neurobiol. 2009;19(3):298-304. [Crossref]  [PubMed]  [PMC] 
  7. Wimmer ME, Blackwell JM, Abel T. Rolipram treatment during consolidation ameliorates long-term object location memory in aged male mice. Neurobiol Learn Mem. 2020;169:107168. [Crossref]  [PubMed]  [PMC] 
  8. Nagakura A, Niimura M, Takeo S. Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism-induced defects in memory function and cerebral cyclic AMP signal transduction system in rats. Br J Pharmacol. 2002;135(7):1783-93. [Crossref]  [PubMed]  [PMC] 
  9. Nikulina E, Tidwell JL, Dai HN, Bregman BS, Filbin MT. The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A. 2004;101(23):8786-90. [Crossref]  [PubMed]  [PMC] 
  10. Luo Y, Wu X, Liu S, Li K. Reactivation of visual cortical plasticity by NEP1-40 from early monocular deprivation in adult rats. Neurosci Lett. 2011;494(3):196-201. [Crossref]  [PubMed] 
  11. Hannila SS, Filbin MT. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp Neurol. 2008;209(2):321-32. [Crossref]  [PubMed]  [PMC] 
  12. Gao Y, Nikulina E, Mellado W, Filbin MT. Neurotrophins elevate cAMP to reach a threshold required to overcome inhibition by MAG through extracellular signal-regulated kinase-dependent inhibition of phosphodiesterase. J Neurosci. 2003;23(37):11770-7. [Crossref]  [PubMed]  [PMC] 
  13. Zhuo Y, Guo H, Cheng Y, Wang C, Wang C, Wu J, et al. Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25-35 in rats. Metab Brain Dis. 2016;31(4):779-91. [Crossref]  [PubMed] 
  14. Maher A, El Sayed N, Nafea H, Gad M. Rolipram rescues memory consolidation deficits caused by sleep deprivation: implication of the cAMP/PKA and cAMP/Epac pathways. CNS Neurol Disord Drug Targets. 2022;21(7):631-9. [Crossref]  [PubMed] 
  15. Virk D, Kumar A, Jaggi AS, Singh N. Ameliorative role of rolipram, PDE-4 inhibitor, against sodium arsenite-induced vascular dementia in rats. Environ Sci Pollut Res Int. 2021;28(44):63250-62. [Crossref]  [PubMed] 
  16. Zhong Y, Zhu Y, He T, Li W, Yan H, Miao Y. Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels. Neurosci Lett. 2016;610:171-6. [Crossref]  [PubMed] 
  17. Bach ME, Barad M, Son H, Zhuo M, Lu YF, Shih R, et al. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci U S A. 1999;96(9):5280-5. [Crossref]  [PubMed]  [PMC] 
  18. Navakkode S, Sajikumar S, Frey JU. The type IV-specific phosphodiesterase inhibitor rolipram and its effect on hippocampal long-term potentiation and synaptic tagging. J Neurosci. 2004;24(35):7740-4. [Crossref]  [PubMed]  [PMC] 
  19. Maffei A, Nelson SB, Turrigiano GG. Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation. Nat Neurosci. 2004;7(12):1353-9. [Crossref]  [PubMed] 
  20. Prusky GT, West PW, Douglas RM. Experience-dependent plasticity of visual acuity in rats. Eur J Neurosci. 2000;12(10):3781-6. [Crossref]  [PubMed] 
  21. Spolidoro M, Putignano E, Munafò C, Maffei L, Pizzorusso T. Inhibition of matrix metalloproteinases prevents the potentiation of nondeprived-eye responses after monocular deprivation in juvenile rats. Cereb Cortex. 2012;22(3):725-34. [Crossref]  [PubMed] 
  22. Freeman S, Sohmer H. Effect of thyroxine on the development of somatosensory and visual evoked potentials in the rat. J Neurol Sci. 1995;128(2):143-50. [Crossref]  [PubMed] 
  23. Jones DG, Devon RM. An ultrastructural study into the effects of pentobarbitone on synaptic organization. Brain Res. 1978;147(1):47-63. [Crossref]  [PubMed] 
  24. Güldner FH, Ingham CA. Increase in postsynaptic density material in optic target neurons of the rat suprachiasmatic nucleus after bilateral enucleation. Neurosci Lett. 1980;17(1-2):27-31. [Crossref]  [PubMed] 
  25. Xiao Y, Fu H, Han X, Hu X, Gu H, Chen Y, et al. Role of synaptic structural plasticity in impairments of spatial learning and memory induced by developmental lead exposure in Wistar rats. PLoS One. 2014;9(12):e115556. [Crossref]  [PubMed]  [PMC] 
  26. Meyer D, Bonhoeffer T, Scheuss V. Balance and stability of synaptic structures during synaptic plasticity. Neuron. 2014;82(2):430-43. Erratum in: Neuron. Jun 4;82(5):1188. [Crossref]  [PubMed] 
  27. Engert F, Bonhoeffer T. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature. 1999;399(6731):66-70. [Crossref]  [PubMed] 
  28. Xu L, Li Z, Rong J, Lang L. Effect of regulation of the NRG1/ErbB4 signaling pathway on the visual cortex synaptic plasticity of amblyopic adult rats. J Biochem Mol Toxicol. 2021;35(9):e22841. [Crossref]  [PubMed] 
  29. Giorgi M, Modica A, Pompili A, Pacitti C, Gasbarri A. The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task. Behav Brain Res. 2004;154(1):99-106. [Crossref]  [PubMed] 
  30. O'Donnell JM, Frith S. Behavioral effects of family-selective inhibitors of cyclic nucleotide phosphodiesterases. Pharmacol Biochem Behav. 1999;63(1):185-92. [Crossref]  [PubMed] 
  31. Rock EM, Benzaquen J, Limebeer CL, Parker LA. Potential of the rat model of conditioned gaping to detect nausea produced by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. Pharmacol Biochem Behav. 2009;91(4):537-41. [Crossref]  [PubMed] 
  32. Gobejishvili L, Rodriguez WE, Bauer P, Wang Y, Soni C, Lydic T, et al. Novel liposomal rolipram formulation for clinical application to reduce emesis. Drug Des Devel Ther. 2022;16:1301-9. [Crossref]  [PubMed]  [PMC] 
  33. Teixeira MM, Gristwood RW, Cooper N, Hellewell PG. Phosphodiesterase (PDE)4 inhibitors: anti-inflammatory drugs of the future? Trends Pharmacol Sci. 1997;18(5):164-71. [Crossref]  [PubMed] 
  34. Yuste R, Bonhoeffer T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci. 2001;24:1071-89. [Crossref]  [PubMed] 

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