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Distal axonopathy with structural persistence in glaucomatous neurodegeneration.

ABSTRACT: An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport deficits increases with age and is not necessarily associated with elevated ocular pressure. Transport deficits progress distal-to-proximal, appearing in the colliculus first followed by more proximal secondary targets and then the optic tract. Transport persists through the optic nerve head before finally failing in the retina. Although axon degeneration also progresses distal-to-proximal, myelinated RGC axons and their presynaptic terminals persist in the colliculus well after transport fails. Thus, distal transport loss is predegenerative and may represent a therapeutic target.

SUBMITTER: Crish SD

PROVIDER: S-EPMC2841892 | biostudies-other | 2010 Mar

REPOSITORIES: biostudies-other

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Distal axonopathy with structural persistence in glaucomatous neurodegeneration.

Crish Samuel D SD Sappington Rebecca M RM Inman Denise M DM Horner Philip J PJ Calkins David J DJ

Proceedings of the National Academy of Sciences of the United States of America 20100301 11

An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the degeneration of retinal ganglion cell (RGC) neurons and their axons in the optic nerve. Here we show that, like other neurodegenerations, distal axon injury appears early in mouse glaucoma. Where RGC axons terminate in the superior colliculus, reduction of active transport follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to transport defici ...[more]

PMID: 20194762

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Project description:BackgroundThe nasal to temporal amplitudes ratio (N/T) of multifocal electroretinography (mfERG) scans measured within 5° of the macula can be used to detect glaucomatous change. The photopic negative response (PhNR) of mfERG elicited by a circular stimulus centered on the fovea was significantly reduced in eyes with glaucoma. The PhNR to B-wave ratio (PhNR/B) is the optimal measure of the PhNR. However, clinical superiority for evaluating glaucoma patients has not been determined between N/T and PhNR/B yet.MethodsFor morphological assessments, ganglion cell complex (GCC) in six regions and the average were measured by optical coherence tomography (OCT). For functional assessment, Humphrey visual fields (VF) with mean sensitivities (MT) and mfERG scans with parameters of N/T and the multifocal photopic negative response to B-wave ratio (mfPhNR/B) were measured. Sixty-nine eyes of 44 glaucoma patients were included and correlations between mfERG parameters and OCT or VF parameters were evaluated.ResultsThe mean age of patients was 59.4 years. The mean deviation for all eyes obtained with the VF 30-2 and VF 10-2 was - 7.00 and - 6.31 dB, respectively. Significant correlations between GCC thickness or VF parameter and the N/T were found, especially in the inferior and inforotemporal retinal areas corresponding to superior and superonasal VF sectors (GCC vs N/T; coefficient = - 7.916 and - 7.857, and MT vs N/T; coefficient = - 4.302 and - 4.437, in the inferior and inforotemporal retinal areas, respectively, all p values < 0.05). However, similar associations were not obtained between mfPhNR/B and OCT or VF parameters. The mfPhNR/B only in the inferotemporal sector was significantly correlated with the average thickness of GCC (coefficient = 4.823, P = 0.012).ConclusionsThe N/T was correlated with GCC and VF in more numbers of measurement areas than the mfPhNR/B in the current study, however, a future study modifying the stimuli and amplitudes to obtain the spatial correspondence to OCT and VF measurement will be required to evaluate the value of mfERG.

Project description:Importance:Both parapapillary and macular areas are important in determining the progression of early glaucoma. However, no attempt has been made to assess the progression of glaucoma in images that combine the 2 areas. Objective:To evaluate the potential usefulness of serial analysis of combined wide-field optical coherence tomography (OCT) maps for detection of structural progression in patients with early glaucoma. Design, Setting, and Participants:Retrospective observational study. Patients with early primary open-angle glaucoma with a minimum of 3-year follow-up involving serial spectral-domain OCT measurement were analyzed. Patients were divided into a nonprogressor group (n?=?47) and a progressor group (n?=?47) on the basis of serial stereo disc photography and red-free photography. Serial combined wide-field OCT maps integrating parapapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) maps were generated with the embedded software of serial spectral-domain OCT. Glaucoma specialists then assessed the structural progression detection ability of those serial wide-field OCT maps for early glaucomatous eyes and compared their sensitivity with those of RNFL and GCIPL guided progression analyses (GPAs). Main Outcomes and Measures:The diagnostic ability of the serial wide-field OCT maps for early glaucomatous structural progression. Results:Ninety-four patients (mean [SD] age, 51.4?[12.3] years; 48 [51.1%] women; all Korean) were included. The serial wide-field OCT map analysis showed good agreement for detection of structural progression between the 2 glaucoma graders (wide-field OCT thickness map: ??=?0.649; wide-field OCT deviation map: ??=?0.833). These maps showed early glaucomatous structural progression detection abilities comparable with those of RNFL and GCIPL GPAs (sensitivities of wide-field OCT thickness map, wide-field OCT deviation map, RNFL GPA, and GCIPL GPA?=?63.8%, 83.0%, 83.0%, and 66.0%, respectively, all P?>?.05; specificities of wide-field OCT thickness map, wide-field OCT deviation map, RNFL GPA, and GCIPL GPA?=?93.6%, 95.7%, 84.8%, and 93.6%, respectively, all P?>?.05). Conclusions and Relevance:The serial combined wide-field OCT maps integrating RNFL and GCIPL maps performed well in detecting structural progression in early glaucomatous eyes. Confirmation in an independent prospective study might provide greater confidence in this conclusion.

Dataset Information

Distal axonopathy with structural persistence in glaucomatous neurodegeneration.

Publications

Distal axonopathy with structural persistence in glaucomatous neurodegeneration.

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