Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involveme...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Public Library of Science
2012
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507727/ |
| id |
pubmed-3507727 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-35077272012-12-03 Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy Rizzo, Giovanni Tozer, Kevin R. Tonon, Caterina Manners, David Testa, Claudia Malucelli, Emil Valentino, Maria Lucia La Morgia, Chiara Barboni, Piero Randhawa, Ruvdeep S. Ross-Cisneros, Fred N. Sadun, Alfredo A. Carelli, Valerio Lodi, Raffaele Research Article Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05) and lack of recovery of visual acuity (B = 0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons. Public Library of Science 2012-11-27 /pmc/articles/PMC3507727/ /pubmed/23209682 http://dx.doi.org/10.1371/journal.pone.0050230 Text en © 2012 Rizzo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Rizzo, Giovanni Tozer, Kevin R. Tonon, Caterina Manners, David Testa, Claudia Malucelli, Emil Valentino, Maria Lucia La Morgia, Chiara Barboni, Piero Randhawa, Ruvdeep S. Ross-Cisneros, Fred N. Sadun, Alfredo A. Carelli, Valerio Lodi, Raffaele |
| spellingShingle |
Rizzo, Giovanni Tozer, Kevin R. Tonon, Caterina Manners, David Testa, Claudia Malucelli, Emil Valentino, Maria Lucia La Morgia, Chiara Barboni, Piero Randhawa, Ruvdeep S. Ross-Cisneros, Fred N. Sadun, Alfredo A. Carelli, Valerio Lodi, Raffaele Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| author_facet |
Rizzo, Giovanni Tozer, Kevin R. Tonon, Caterina Manners, David Testa, Claudia Malucelli, Emil Valentino, Maria Lucia La Morgia, Chiara Barboni, Piero Randhawa, Ruvdeep S. Ross-Cisneros, Fred N. Sadun, Alfredo A. Carelli, Valerio Lodi, Raffaele |
| author_sort |
Rizzo, Giovanni |
| title |
Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| title_short |
Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| title_full |
Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| title_fullStr |
Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| title_full_unstemmed |
Secondary Post-Geniculate Involvement in Leber’s Hereditary Optic Neuropathy |
| title_sort |
secondary post-geniculate involvement in leber’s hereditary optic neuropathy |
| description |
Leber’s hereditary optic neuropathy (LHON) is characterized by retinal ganglion cell (RGC) degeneration with the preferential involvement of those forming the papillomacular bundle. The optic nerve is considered the main pathological target for LHON. Our aim was to investigate the possible involvement of the post-geniculate visual pathway in LHON patients. We used diffusion-weighted imaging for in vivo evaluation. Mean diffusivity maps from 22 LHON visually impaired, 11 unaffected LHON mutation carriers and 22 healthy subjects were generated and compared at level of optic radiation (OR). Prefrontal and cerebellar white matter were also analyzed as internal controls. Furthermore, we studied the optic nerve and the lateral geniculate nucleus (LGN) in post-mortem specimens obtained from a severe case of LHON compared to an age-matched control. Mean diffusivity values of affected patients were higher than unaffected mutation carriers (P<0.05) and healthy subjects (P<0.01) in OR and not in the other brain regions. Increased OR diffusivity was associated with both disease duration (B = 0.002; P<0.05) and lack of recovery of visual acuity (B = 0.060; P<0.01). Post-mortem investigation detected atrophy (41.9% decrease of neuron soma size in the magnocellular layers and 44.7% decrease in the parvocellular layers) and, to a lesser extent, degeneration (28.5% decrease of neuron density in the magnocellular layers and 28.7% decrease in the parvocellular layers) in the LHON LGN associated with extremely severe axonal loss (99%) in the optic nerve. The post-geniculate involvement in LHON patients is a downstream post-synaptic secondary phenomenon, reflecting de-afferentation rather than a primary neurodegeneration due to mitochondrial dysfunction of LGN neurons. |
| publisher |
Public Library of Science |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507727/ |
| _version_ |
1611935858596773888 |