Morphometric, immunohistochemical and ultrastructural examination of age-related structural alterations in optic nerve

Year 2024, , 416 - 425, 30.07.2024

Serpil Çilingiroğlu Anlı , Engin Çalgüner , Deniz Erdoğan , Dural Kadıoğlu Çiğdem Elmas , Rabet Gozil , Meltem Bahçelioğlu

https://doi.org/10.32322/jhsm.1486594

Abstract

Aims: As individuals age, there is a known decline in visual function attributed to a reduction in the optic nerve fibers and myelin sheath degeneration. Studies present conflicting findings on whether aging affects axonal integrity in the human optic nerve. This study aims to investigate degenerative changes in the aging rat optic nerve.
Methods: The investigation involved 36 Wistar albino rats. The rats were divided into six groups: the newborn, prepubertal, pubertal, junior, adult, and elderly groups. This study investigated optic nerve axon counts, axon diameters, levels of glial fibrillary acidic protein immunoreactivity (GFAP-IR) and nerve growth factor immunoreactivity (NGF-IR), as well as findings from light microscopy (LM) and electron microscopy (EM) in these groups.
Results: This study observed age-related alterations in rat optic nerves, including increased diameter, irregular axon count fluctuations (both increases and decreases), elevated astrocyte count, and a simultaneous decline in oligodendrocyte count. Additionally, it was observed that NGF-IR was predominantly at the membrane level in newborns and moderately in the cytoplasm, whereas in older ages, it was evident at both cellular and axonal levels furthermore, it was observed that GFAP-IR increased with age. However, in LM and EM examinations, axonal loss and rarefaction, accumulation of osmiophilic substances, splitting of the myelin sheath, vacuolization, axonal retraction were observed.
Conclusion: In this study, it was found that one of the causes of age-related vision loss is the advanced degenerative changes in the optic nerve and it was concluded that the remaining small-diameter myelinated nerve fibers may partially compensate for the sense of vision. Our study reveals that age-related degenerative changes in the central nervous system resemble those in multiple sclerosis (MS), suggesting a potential contribution to MS pathogenesis.

Keywords

Optic nerve, age-related changes, nerve growth factor, glial fibrillary acidic protein, electron microscopy, multiple sclerosis

Ethical Statement

The study obtained ethical approval from the Ethics Committee of Gazi University on November 9, 2004, with reference number 15517 and code number GÜTF-04.030.

Supporting Institution

Gazi Üniversitesi'nin Bilimsel Araştırma Projesi'nden destek alındı.

Thanks

We would like to express our sincere gratitude to Prof. Dr. Bulent BAKAR, Department of Neurosurgery, Kirikkale University Faculty of Medicine for his invaluable guidance, insightful suggestions, and unwavering support throughout the course of this research. With gratitude, we express our appreciation to Dr. Bahar Kartal for her invaluable contributions to the immunohistochemical evaluations presented in the manuscript.

References

• De Moraes CG. Anatomy of the visual pathways. J Glaucoma. 2013;(22)5:2-7. doi: 10.1097/IJG.0b013e3182934978
• Shao Y, Li L, Peng W, Lu W, Wang Y. Age-related changes in the healthy adult visual pathway: evidence from diffusion tensor imaging with fixel-based analysis. Radiologie (Heidelb). 2023;63(2):73-81. doi: 10.1007/s00117-023-01192-x
• Trinh M, Kalloniatis M, Alonso-Caneiro D, Nivison-Smith L. High-density optical coherence tomography analysis provides insights into early/intermediate age-related macular degeneration retinal layer changes. Invest Ophthalmol Vis Sci. 2022;63(5):36. doi: 10.1167/iovs.63.5.36
• Balazsi AG, Rootman J, Drance SM, Schulzer M, Douglas GR. The effect of age on the nerve fiber population of the human optic nerve. Am J Ophthalmol. 1984;97(6):760-766. doi: 10.1016/0002-9394(84)90509-9
• Vrabec F. Age changes of the human optic nerve head. A neurohistologic study. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1977;202(3):231-236. doi: 10.1007/BF00407873
• Dolman CL, McCormick AQ, Drance SM. Aging of the optic nerve. Arch Ophthalmol. 1980;98(11):2053-2058. doi: 10.1001/archopht.1980.01020040905024
• Repka MX, Quigley HA. The effect of age on normal human optic nerve fiber number and diameter. Ophthalmology. 1989;96(1):26-32. doi: 10.1016/s0161-6420(89)32928-9
• Cavallotti C, Cavallotti D, Pescosolido N, Pacella E. Age-related changes in rat optic nerve: morphological studies. Anat Histol Embryol. 2003;32(1):12-16. doi: 10.1046/j.1439-0264.2003.00431.x
• El-Sayyad HI, Khalifa SA, El-Sayyad FI, Al-Gebaly AS, El-Mansy AA, Mohammed EA. Aging-related changes of optic nerve of Wistar albino rats. Age (Dordr). 2014;36(2):519-532. doi: 10.1007/s11357-013-9580-5
• Godlewski A. Morphometry of myelin fibers in corpus callosum and optic nerve of aging rats. J Hirnforsch. 1991;32(1):39-46.
• Sandell JH, Peters A. Effects of age on the glial cells in the rhesus monkey optic nerve. J Comp Neurol. 2002;445(1):13-28. doi: 10.1002/cne.10162
• Cavallotti C, Pacella E, Pescosolido N, Tranquilli-Leali FM, Feher J. Age-related changes in the human optic nerve. Can J Ophthalmol. 2002;37(7):389-394. doi: 10.1016/s0008-4182(02)80040-0
• Yew DT. Aging in retinas and optic nerves of 2.5- to 9-month-old mice. Acta Anat (Basel). 1979;104(3):332-334. doi: 10.1159/000145079
• Sing NM, Anderson SF, Townsend JC. The normal optic nerve head. Optom Vis Sci. 2000;77(6):293-301. doi: 10.1097/00006324-200006000-00009
• Trapp BD, Nave KA. Multiple Sclerosis: an immune or neurodegenerative disorder? Annual Rev Neurosci. 2008;31:247-269. doi: 10.1146/annurev.neuro.30.051606.094313
• Ricci A, Bronzetti E, Amenta F. Effect of ageing on the nerve fibre population of rat optic nerve. Gerontology. 1988;34(5-6): 231-235. doi: 10.1159/000212960
• Fox JG, Cohen BJ, Loew FM. Laboratory animal medicine. USA Academic Pres. 1984:95.
• Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21(20):3798-3807. doi: 10.1200/JCO.2003.11.069  
• Kiyosawa I. Age-related changes in visual function and visual organs of rats. Exp Anim. 1996;45(2):103-114. doi: 10.1538/expanim.45.103
• Sturrock RR. Changes in the number of axons in the human embryonic optic nerve from 8 to 18 weeks gestation. J Hirnforsch. 1987;28(6):649-652.
• Butt AM, Kirvell S. Glial cells in transected optic nerves of immature rats. II. an immunohistochemical study. J Neurocytol. 1996;25(6):381-392. doi: 10.1007/BF02284809
• Attia H, Taha M, Abdellatif A. Effects of aging on the myelination of the optic nerve in rats. Int J Neurosci. 2019;129(4):320-324. doi: 10.1080/00207454.2018.1529670
• Yassa HD. Age-related changes in the optic nerve of Sprague-Dawley rats: an ultrastructural and immunohistochemical study. Acta Histochem. 2014;116(6):1085-1095. doi: 10.1016/j.acthis. 2014.05.001
• Lam K, Sefton AJ, Bennett MR. Loss of axons from the optic nerve of the rat during early postnatal development. Brain Res. 1982;255(3):487-491. doi: 10.1016/0165-3806(82)90014-1
• Wong SL, Ip PP, Yew DT. Comparative ultrastructural study of the optic nerves and visual cortices of young (2.5 months) and old (17 months) mice. Acta Anat (Basel). 1979;105(4):426-430. doi: 10.1159/000145149
• Triviño A, Ramírez JM, Salazar JJ, Ramírez AI, García-Sánchez J. Immunohistochemical study of human optic nerve head astroglia. Vision Res. 1996;36(14):2015-2028. doi: 10.1016/0042-6989(95)00317-7
• Hernandez MR, Igoe F, Neufeld AH. Extracellular matrix of the human optic nerve head. Am J Ophthalmol. 1986;102(2):139-148. doi: 10.1016/0002-9394(86)90134-0
• Hernandez MR, Luo XX, Andrzejewska W, Neufeld AH. Age-related changes in the extracellular matrix of the human optic nerve head. Am J Ophthalmol. 1989;107(5):476-484. doi: 10.1016/0002-9394(89)90491-1
• Cepurna WO, Kayton RJ, Johnson EC, Morrison JC. Age related optic nerve axonal loss in adult Brown Norway rats. Exp Eye Res. 2005;80(6):877-884. doi: 10.1016/j.exer.2004.12.021
• Gabilondo I, Martínez-Lapiscina EH, Martinez-Heras E, et al. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol. 2014;75(1):98-107. doi: 10.1002/ana.24030
• Tur C, Goodkin O, Altmann DR, et al. Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis. Brain. 2016;139(3):816-828. doi: 10.1093/brain/awv396
• Compston A, Coles A. Multiplesclerosis. Lancet. 2008;372(9648): 1502-1517. doi: 10.1016/S0140-6736(08)61620-7
• Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000;47(6):707-717. doi: 10.1002/1531-8249(200006)47:6<707:aid-ana3>3.0.co;2-q
• Compston DAS. McAlpine’s multiple sclerosis. 4th edn. London: Elsevier, 2005:589.
• Skoff RP, Toland D, Nast E. Pattern of myelination and distribution of neuroglial cells along the developing optic system of the rat and rabbit. J Comp Neurol. 1980;191(2):237-253. doi: 10.1002/cne.901910207