Advances in transsynaptic retrograde degeneration of optic neuropathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Huo Yan , Lin Xuemei ,  Wu Songdi

Department of Neuro-Ophthalmology, The First Affiliated Hospital of Northwestern University (The First Hospital of Xi’an), Xi’an 710002, China;

Corresponding author：

Wu Songdi, Email: wusongdi@gmail.com

Keywords：

Transsynaptic retrograde degeneration of optic neuropathy; Retinal ganglion cells; Visual field defect; Atrophy of optic tract; Review

DOI：

10.3760/cma.j.cn511434-20220930-00517

Video：

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Transsynaptic retrograde degeneration of optic neuropathy (TRDON) refers to the degeneration and/or apoptosis of presynaptic neurons (retinal ganglion cells) caused by damage to the lateral geniculate body and post-geniculate visual pathway. At present, the pathogenesis of TRDON is secondary apoptosis of P_β-type retinal ganglion cells, resulting in the atrophy of optic tract, thinning of the retinal nerve fiber layer and retinal ganglion cell layer thickness and declining of retinal microvascular density, which are consistent with the visual field defect attributed to the primary disease. Of which, the thinning of the retinal ganglion cell layer thickness is considered as the characteristic of TRDON. Now, there is little understanding and related research on TRDON in China. Clinicians should pay attention to the characteristics and severity, occurrence time and location of the above structural changes in these patients through optical coherence tomography, and monitor the activity and progress of the lesions, so as to determine the cut-off point for drug intervention and the drug targets for developing new treatment methods, and bring benefits for patients in partial visual function recovery and disability reduction.

Citation： Huo Yan, Lin Xuemei, Wu Songdi. Advances in transsynaptic retrograde degeneration of optic neuropathy. Chinese Journal of Ocular Fundus Diseases, 2022, 38(12): 1035-1038. doi: 10.3760/cma.j.cn511434-20220930-00517 Copy

1.	Dinkin M. Trans-synaptic retrograde degeneration in the human visual system: slow, silent, and real[J]. Curr Neurol Neurosci Rep, 2017, 17(2): 16. DOI: 10.1007/s11910-017-0725-2.
2.	Beatty RM, Sadun AA, Smith L, et al. Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes[J]. J Neurol Neurosurg Psychiatry, 1982, 45(2): 143-146. DOI: 10.1136/jnnp.45.2.143.
3.	Sharma S, Chitranshi N, Wall RV, et al. Trans-synaptic degeneration in the visual pathway: neural connectivity, pathophysiology, and clinical implications in neurodegenerative disorders[J]. Surv Ophthalmol, 2022, 67(2): 411-426. DOI: 10.1016/j.survophthal.2021.06.001.
4.	毛俊峰, 魏世辉. 逆行跨突触变性视神经病变的研究现状[J]. 国际眼科纵览, 2016, 40(6): 405-408. DOI: 10.3760/cma.j.issn.1673-5803.2016.06.010.Mao JF, Wei SH. Research status of transsynaptic retrograde degenerating optic neuropathy[J]. Int Rev Ophthalmol, 2016, 40(6): 405-408. DOI: 10.3760/cma.j.issn.1673-5803.2016.06.010.
5.	Keller J, Sánchez-Dalmau BF, Villoslada P. Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells[J/OL]. PLoS One, 2014, 9(5): e97444 [2014-05-23]. https://pubmed.ncbi.nlm.nih.gov/24857938/. DOI: 10.1371/journal.pone.0097444.
6.	Lennartsson F, Nilsson M, Flodmark O, et al. Injuries to the immature optic radiation show correlated thinning of the macular ganglion cell layer[J]. Front Neurol, 2018, 9: 321. DOI: 10.3389/fneur.2018.00321.
7.	Balk LJ, Steenwijk MD, Tewarie P, et al. Bidirectional trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis[J]. J Neurol Neurosurg Psychiatry, 2015, 86(4): 419-424. DOI: 10.1136/jnnp-2014-308189.
8.	Fahrenthold BK, Cavanaugh MR, Jang S, et al. Optic tract shrinkage limits visual restoration after occipital stroke[J]. Stroke, 2021, 52(11): 3642-3650. DOI: 10.1161/STROKEAHA.121.034738.
9.	Kanamori A, Nakamura M, Matsui N, et al. Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs[J]. Ophthalmology, 2004, 111(12): 2278-2283. DOI: 10.1016/j.ophtha.2004.05.035.
10.	Guedes ME, Almeida AC, Patricio MS, et al. Acquired retrograde transsynaptic degeneration[J/OL]. BMJ Case Rep, 2011, 2011: bcr0820114653[2011-09-28]. https://pubmed.ncbi.nlm.nih.gov/22679330/. DOI: 10.1136/bcr.08.2011.4653.
11.	Patel KR, Ramsey LE, Metcalf NV, et al. Early diffusion evidence of retrograde transsynaptic degeneration in the human visual system[J]. Neurology, 2016, 87(2): 198-205. DOI: 10.1212/WNL.0000000000002841.
12.	Jindahra P, Petrie A, Plant GT. Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography[J]. Brain, 2009, 132(Pt 3): 628-634. DOI:10.1093/brain/awp001.
13.	Jindahra P, Petrie A, Plant GT. The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans[J]. Brain, 2012, 135(Pt 2): 534-541. DOI: 10.1093/brain/awr324.
14.	Lee JI, Boerker L, Gemerzki L, et al. Retinal changes after posterior cerebral artery infarctions display different patterns of the nasal und temporal sector in a case series[J]. Front Neurol, 2020, 11: 508. DOI: 10.3389/fneur.2020.00508.
15.	Meier P, Maeder P, Borruat FX. Transsynaptic retrograde degeneration: clinical evidence with homonymous RGCL loss on OCT[J]. Klin Monbl Augenheilkd, 2016, 233(4): 396-398. DOI: 10.1055/s-0041-111535.
16.	Vien L, DalPorto C, Yang D. Retrograde degeneration of retinal ganglion cells secondary to head trauma[J]. Optom Vis Sci, 2017, 94(1): 125-134. DOI: 10.1097/OPX.0000000000000899.
17.	Schwartz SG, Pasol J, Lam BL, et al. Spectral-domain optical coherence tomography documentation of transsynaptic retinal degeneration[J]. Ophthalmic Surg Lasers Imaging Retina, 2016, 47(8): 768-772. DOI: 10.3928/23258160-20160808-11.
18.	Meier PG, Maeder P, Kardon RH, et al. Homonymous ganglion cell layer thinning after isolated occipital lesion: macular OCT demonstrates transsynaptic retrograde retinal degeneration[J]. J Neuroophthalmol, 2015, 35(2): 112-116. DOI: 10.1097/WNO.0000000000000182.
19.	Yamashita T, Miki A, Goto K, et al. Evaluation of significance maps and the analysis of the longitudinal time course of the macular ganglion cell complex thicknesses in acquired occipital homonymous hemianopia using spectral-domain optical coherence tomography[J]. Neuroophthalmology, 2019, 44(4): 236-245. DOI: 10.1080/01658107.2019.1686764.
20.	Mitchell JR, Oliveira C, Tsiouris AJ, et al. Corresponding ganglion cell atrophy in patients with postgeniculate homonymous visual field loss[J]. J Neuroophthalmol, 2015, 35(4): 353-359. DOI: 10.1097/WNO.0000000000000268.
21.	Goto K, Miki A, Yamashita T, et al. Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography[J]. Graefe's Arch Clin Exp Ophthalmol, 2016, 254(4): 745-756. DOI: 10.1007/s00417-015-3181-1.
22.	Lujan BJ, Horton JC. Microcysts in the inner nuclear layer from optic atrophy are caused by retrograde trans-synaptic degeneration combined with vitreous traction on the retinal surface[J/OL]. Brain, 2013, 136(Pt 11): e260[2013-07-19]. https://pubmed.ncbi.nlm.nih.gov/23872368/. DOI: 10.1093/brain/awt154.
23.	Ghasemi Falavarjani K, Al-Sheikh M, Darvizeh F, et al. Retinal vessel calibre measurements by optical coherence tomography angiography[J]. Br J Ophthalmol, 2017, 101(7): 989-992. DOI: 10.1136/bjophthalmol-2016-309678.
24.	Pellegrini F, Interlandi E, Pichi F, et al. Retrogeniculate lesion of the visual pathways: retinal optical coherence tomography angiography shows evidence of transsynaptic retrograde degeneration[J]. Neuroophthalmology, 2019, 44(2): 114-117. DOI: 10.1080/01658107.2019.1617748.
25.	Jaumandreu L, Sánchez-Gutiérrez V, Muñoz-Negrete FJ, et al. Reduced peripapillary and macular vessel density in unilateral postgeniculate lesions with retrograde transsynaptic degeneration[J]. J Neuroophthalmol, 2019, 39(4): 462-469. DOI: 10.1097/WNO.0000000000000794.
26.	Celik Buyuktepe T, Bingöl Kızıltunç P, Buyuktepe M, et al. Direct and transsynaptic retrograde degeneration and optic nerve head microvascular changes in patients with hemianopia[J]. Eur J Ophthalmol, 2021, 31(4): 1785-1794. DOI: 10.1177/1120672120951731.
27.	Molero-Senosiain M, Vidal-Villegas B, Pascual-Prieto J, et al. Correlation between retrograde trans-synaptic degeneration of ganglion cells and optical coherence tomography angiography following ischemic stroke[J/OL]. Cureus, 2021, 13(11): e19788[2021-11-21]. https://pubmed.ncbi.nlm.nih.gov/34956781/. DOI: 10.7759/cureus.19788.
28.	Cowey A, Stoerig P, Perry VH. Transneuronal retrograde degeneration of retinal ganglion cells after damage to striate cortex in macaque monkeys: selective loss of P beta cells[J]. Neuroscience, 1989, 29(1): 65-80. DOI: 10.1016/0306-4522(89)90333-3.
29.	Feng L, Chen H, Yi J, et al. Long-term protection of retinal ganglion cells and visual function by brain-derived neurotrophic factor in mice with ocular hypertension[J]. Invest Ophthalmol Vis Sci, 2016, 57(8): 3793-3802. DOI: 10.1167/iovs.16-19825.
30.	Weber AJ, Viswanáthan S, Ramanathan C, et al. Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury[J]. Invest Ophthalmol Vis Sci, 2010, 51(1): 327-334. DOI: 10.1167/iovs.09-3740.
31.	Schneider CL, Prentiss EK, Busza A, et al. Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent[J/OL]. Proc Biol Sci, 2019, 286(1897): 20182733[2019-02-27].https://pubmed.ncbi.nlm.nih.gov/30963844/. DOI: 10.1098/rspb.2018.2733.
32.	You Y, Joseph C, Wang C, et al. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease[J]. Brain, 2019, 142(2): 426-442. DOI: 10.1093/brain/awy338.

1. Dinkin M. Trans-synaptic retrograde degeneration in the human visual system: slow, silent, and real[J]. Curr Neurol Neurosci Rep, 2017, 17(2): 16. DOI: 10.1007/s11910-017-0725-2.
2. Beatty RM, Sadun AA, Smith L, et al. Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes[J]. J Neurol Neurosurg Psychiatry, 1982, 45(2): 143-146. DOI: 10.1136/jnnp.45.2.143.
3. Sharma S, Chitranshi N, Wall RV, et al. Trans-synaptic degeneration in the visual pathway: neural connectivity, pathophysiology, and clinical implications in neurodegenerative disorders[J]. Surv Ophthalmol, 2022, 67(2): 411-426. DOI: 10.1016/j.survophthal.2021.06.001.
4. 毛俊峰, 魏世辉. 逆行跨突触变性视神经病变的研究现状[J]. 国际眼科纵览, 2016, 40(6): 405-408. DOI: 10.3760/cma.j.issn.1673-5803.2016.06.010.Mao JF, Wei SH. Research status of transsynaptic retrograde degenerating optic neuropathy[J]. Int Rev Ophthalmol, 2016, 40(6): 405-408. DOI: 10.3760/cma.j.issn.1673-5803.2016.06.010.
5. Keller J, Sánchez-Dalmau BF, Villoslada P. Lesions in the posterior visual pathway promote trans-synaptic degeneration of retinal ganglion cells[J/OL]. PLoS One, 2014, 9(5): e97444 [2014-05-23]. https://pubmed.ncbi.nlm.nih.gov/24857938/. DOI: 10.1371/journal.pone.0097444.
6. Lennartsson F, Nilsson M, Flodmark O, et al. Injuries to the immature optic radiation show correlated thinning of the macular ganglion cell layer[J]. Front Neurol, 2018, 9: 321. DOI: 10.3389/fneur.2018.00321.
7. Balk LJ, Steenwijk MD, Tewarie P, et al. Bidirectional trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis[J]. J Neurol Neurosurg Psychiatry, 2015, 86(4): 419-424. DOI: 10.1136/jnnp-2014-308189.
8. Fahrenthold BK, Cavanaugh MR, Jang S, et al. Optic tract shrinkage limits visual restoration after occipital stroke[J]. Stroke, 2021, 52(11): 3642-3650. DOI: 10.1161/STROKEAHA.121.034738.
9. Kanamori A, Nakamura M, Matsui N, et al. Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs[J]. Ophthalmology, 2004, 111(12): 2278-2283. DOI: 10.1016/j.ophtha.2004.05.035.
10. Guedes ME, Almeida AC, Patricio MS, et al. Acquired retrograde transsynaptic degeneration[J/OL]. BMJ Case Rep, 2011, 2011: bcr0820114653[2011-09-28]. https://pubmed.ncbi.nlm.nih.gov/22679330/. DOI: 10.1136/bcr.08.2011.4653.
11. Patel KR, Ramsey LE, Metcalf NV, et al. Early diffusion evidence of retrograde transsynaptic degeneration in the human visual system[J]. Neurology, 2016, 87(2): 198-205. DOI: 10.1212/WNL.0000000000002841.
12. Jindahra P, Petrie A, Plant GT. Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography[J]. Brain, 2009, 132(Pt 3): 628-634. DOI:10.1093/brain/awp001.
13. Jindahra P, Petrie A, Plant GT. The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans[J]. Brain, 2012, 135(Pt 2): 534-541. DOI: 10.1093/brain/awr324.
14. Lee JI, Boerker L, Gemerzki L, et al. Retinal changes after posterior cerebral artery infarctions display different patterns of the nasal und temporal sector in a case series[J]. Front Neurol, 2020, 11: 508. DOI: 10.3389/fneur.2020.00508.
15. Meier P, Maeder P, Borruat FX. Transsynaptic retrograde degeneration: clinical evidence with homonymous RGCL loss on OCT[J]. Klin Monbl Augenheilkd, 2016, 233(4): 396-398. DOI: 10.1055/s-0041-111535.
16. Vien L, DalPorto C, Yang D. Retrograde degeneration of retinal ganglion cells secondary to head trauma[J]. Optom Vis Sci, 2017, 94(1): 125-134. DOI: 10.1097/OPX.0000000000000899.
17. Schwartz SG, Pasol J, Lam BL, et al. Spectral-domain optical coherence tomography documentation of transsynaptic retinal degeneration[J]. Ophthalmic Surg Lasers Imaging Retina, 2016, 47(8): 768-772. DOI: 10.3928/23258160-20160808-11.
18. Meier PG, Maeder P, Kardon RH, et al. Homonymous ganglion cell layer thinning after isolated occipital lesion: macular OCT demonstrates transsynaptic retrograde retinal degeneration[J]. J Neuroophthalmol, 2015, 35(2): 112-116. DOI: 10.1097/WNO.0000000000000182.
19. Yamashita T, Miki A, Goto K, et al. Evaluation of significance maps and the analysis of the longitudinal time course of the macular ganglion cell complex thicknesses in acquired occipital homonymous hemianopia using spectral-domain optical coherence tomography[J]. Neuroophthalmology, 2019, 44(4): 236-245. DOI: 10.1080/01658107.2019.1686764.
20. Mitchell JR, Oliveira C, Tsiouris AJ, et al. Corresponding ganglion cell atrophy in patients with postgeniculate homonymous visual field loss[J]. J Neuroophthalmol, 2015, 35(4): 353-359. DOI: 10.1097/WNO.0000000000000268.
21. Goto K, Miki A, Yamashita T, et al. Sectoral analysis of the retinal nerve fiber layer thinning and its association with visual field loss in homonymous hemianopia caused by post-geniculate lesions using spectral-domain optical coherence tomography[J]. Graefe's Arch Clin Exp Ophthalmol, 2016, 254(4): 745-756. DOI: 10.1007/s00417-015-3181-1.
22. Lujan BJ, Horton JC. Microcysts in the inner nuclear layer from optic atrophy are caused by retrograde trans-synaptic degeneration combined with vitreous traction on the retinal surface[J/OL]. Brain, 2013, 136(Pt 11): e260[2013-07-19]. https://pubmed.ncbi.nlm.nih.gov/23872368/. DOI: 10.1093/brain/awt154.
23. Ghasemi Falavarjani K, Al-Sheikh M, Darvizeh F, et al. Retinal vessel calibre measurements by optical coherence tomography angiography[J]. Br J Ophthalmol, 2017, 101(7): 989-992. DOI: 10.1136/bjophthalmol-2016-309678.
24. Pellegrini F, Interlandi E, Pichi F, et al. Retrogeniculate lesion of the visual pathways: retinal optical coherence tomography angiography shows evidence of transsynaptic retrograde degeneration[J]. Neuroophthalmology, 2019, 44(2): 114-117. DOI: 10.1080/01658107.2019.1617748.
25. Jaumandreu L, Sánchez-Gutiérrez V, Muñoz-Negrete FJ, et al. Reduced peripapillary and macular vessel density in unilateral postgeniculate lesions with retrograde transsynaptic degeneration[J]. J Neuroophthalmol, 2019, 39(4): 462-469. DOI: 10.1097/WNO.0000000000000794.
26. Celik Buyuktepe T, Bingöl Kızıltunç P, Buyuktepe M, et al. Direct and transsynaptic retrograde degeneration and optic nerve head microvascular changes in patients with hemianopia[J]. Eur J Ophthalmol, 2021, 31(4): 1785-1794. DOI: 10.1177/1120672120951731.
27. Molero-Senosiain M, Vidal-Villegas B, Pascual-Prieto J, et al. Correlation between retrograde trans-synaptic degeneration of ganglion cells and optical coherence tomography angiography following ischemic stroke[J/OL]. Cureus, 2021, 13(11): e19788[2021-11-21]. https://pubmed.ncbi.nlm.nih.gov/34956781/. DOI: 10.7759/cureus.19788.
28. Cowey A, Stoerig P, Perry VH. Transneuronal retrograde degeneration of retinal ganglion cells after damage to striate cortex in macaque monkeys: selective loss of P beta cells[J]. Neuroscience, 1989, 29(1): 65-80. DOI: 10.1016/0306-4522(89)90333-3.
29. Feng L, Chen H, Yi J, et al. Long-term protection of retinal ganglion cells and visual function by brain-derived neurotrophic factor in mice with ocular hypertension[J]. Invest Ophthalmol Vis Sci, 2016, 57(8): 3793-3802. DOI: 10.1167/iovs.16-19825.
30. Weber AJ, Viswanáthan S, Ramanathan C, et al. Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury[J]. Invest Ophthalmol Vis Sci, 2010, 51(1): 327-334. DOI: 10.1167/iovs.09-3740.
31. Schneider CL, Prentiss EK, Busza A, et al. Survival of retinal ganglion cells after damage to the occipital lobe in humans is activity dependent[J/OL]. Proc Biol Sci, 2019, 286(1897): 20182733[2019-02-27].https://pubmed.ncbi.nlm.nih.gov/30963844/. DOI: 10.1098/rspb.2018.2733.
32. You Y, Joseph C, Wang C, et al. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease[J]. Brain, 2019, 142(2): 426-442. DOI: 10.1093/brain/awy338.

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