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Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice.
Curr Eye Res. 2015; 40(12):1269-83.CE

Abstract

PURPOSE

Glaucoma is a group of optic neuropathies characterized by the loss of retinal ganglion cells (RGCs). Since ocular hypertension (OHT) is a main risk factor, current therapies are predominantly based on lowering eye pressure. However, a subset of treated patients continues to lose vision. More research into pathological mechanisms underlying glaucoma is therefore warranted in order to develop novel therapeutic strategies. In this study we investigated the impact of OHT from eye to brain in mice.

METHODS

Monocular hypertension (mOHT) was induced in CD-1 mice by laser photocoagulation (LP) of the perilimbal and episcleral veins. The impact on the retina and its main direct target area, the superficial superior colliculus (sSC), was examined via immunostainings for Brn3a, VGluT2 and GFAP. Alterations in neuronal activity in V1 and extrastriate areas V2L and V2M were assessed using in situ hybridization for the activity reporter gene zif268.

RESULTS

Transient mOHT resulted in diffuse and sectorial RGC degeneration. In the sSC contralateral to the OHT eye, a decrease in VGluT2 immunopositive synaptic connections was detected one week post LP, which appeared to be retinotopically linked to the sectorial RGC degeneration patterns. In parallel, hypoactivity was discerned in contralateral retinotopic projection zones in V1 and V2. Despite complete cortical reactivation 4 weeks post LP, in the sSC no evidence for recovery of RGC synapse density was found and also the concomitant inflammation was not completely resolved. Nevertheless, sSC neurons appeared healthy upon histological inspection and subsequent analysis of cell density revealed no differences between the ipsi- and contralateral sSC.

CONCLUSION

In addition to RGC death, OHT induces loss of synaptic connections and neuronal activity in the visual pathway and is accompanied by an extensive immune response. Our findings stress the importance of looking beyond the eye and including the whole visual system in glaucoma research.

Authors+Show Affiliations

a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.c Department of Ophthalmology , University of Murcia and IMIB-Arrixaca , Murcia , Spain.a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .c Department of Ophthalmology , University of Murcia and IMIB-Arrixaca , Murcia , Spain.b Laboratory of Neuroplasticity and Neuroproteomics, Department of Biology , KU Leuven , Leuven , Belgium and.a Neural Circuit Development and Regeneration Research Group, Department of Biology, KU Leuven , Leuven , Belgium .

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25615273

Citation

Dekeyster, Eline, et al. "Ocular Hypertension Results in Retinotopic Alterations in the Visual Cortex of Adult Mice." Current Eye Research, vol. 40, no. 12, 2015, pp. 1269-83.
Dekeyster E, Aerts J, Valiente-Soriano FJ, et al. Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice. Curr Eye Res. 2015;40(12):1269-83.
Dekeyster, E., Aerts, J., Valiente-Soriano, F. J., De Groef, L., Vreysen, S., Salinas-Navarro, M., Vidal-Sanz, M., Arckens, L., & Moons, L. (2015). Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice. Current Eye Research, 40(12), 1269-83. https://doi.org/10.3109/02713683.2014.990983
Dekeyster E, et al. Ocular Hypertension Results in Retinotopic Alterations in the Visual Cortex of Adult Mice. Curr Eye Res. 2015;40(12):1269-83. PubMed PMID: 25615273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice. AU - Dekeyster,Eline, AU - Aerts,Jeroen, AU - Valiente-Soriano,Francisco Javier, AU - De Groef,Lies, AU - Vreysen,Samme, AU - Salinas-Navarro,Manuel, AU - Vidal-Sanz,Manuel, AU - Arckens,Lutgarde, AU - Moons,Lieve, Y1 - 2015/01/23/ PY - 2015/1/24/entrez PY - 2015/1/24/pubmed PY - 2016/7/7/medline KW - Glaucoma KW - ocular hypertension KW - retinal ganglion cell KW - superior colliculus KW - visual cortex SP - 1269 EP - 83 JF - Current eye research JO - Curr Eye Res VL - 40 IS - 12 N2 - PURPOSE: Glaucoma is a group of optic neuropathies characterized by the loss of retinal ganglion cells (RGCs). Since ocular hypertension (OHT) is a main risk factor, current therapies are predominantly based on lowering eye pressure. However, a subset of treated patients continues to lose vision. More research into pathological mechanisms underlying glaucoma is therefore warranted in order to develop novel therapeutic strategies. In this study we investigated the impact of OHT from eye to brain in mice. METHODS: Monocular hypertension (mOHT) was induced in CD-1 mice by laser photocoagulation (LP) of the perilimbal and episcleral veins. The impact on the retina and its main direct target area, the superficial superior colliculus (sSC), was examined via immunostainings for Brn3a, VGluT2 and GFAP. Alterations in neuronal activity in V1 and extrastriate areas V2L and V2M were assessed using in situ hybridization for the activity reporter gene zif268. RESULTS: Transient mOHT resulted in diffuse and sectorial RGC degeneration. In the sSC contralateral to the OHT eye, a decrease in VGluT2 immunopositive synaptic connections was detected one week post LP, which appeared to be retinotopically linked to the sectorial RGC degeneration patterns. In parallel, hypoactivity was discerned in contralateral retinotopic projection zones in V1 and V2. Despite complete cortical reactivation 4 weeks post LP, in the sSC no evidence for recovery of RGC synapse density was found and also the concomitant inflammation was not completely resolved. Nevertheless, sSC neurons appeared healthy upon histological inspection and subsequent analysis of cell density revealed no differences between the ipsi- and contralateral sSC. CONCLUSION: In addition to RGC death, OHT induces loss of synaptic connections and neuronal activity in the visual pathway and is accompanied by an extensive immune response. Our findings stress the importance of looking beyond the eye and including the whole visual system in glaucoma research. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/25615273/Ocular_hypertension_results_in_retinotopic_alterations_in_the_visual_cortex_of_adult_mice_ DB - PRIME DP - Unbound Medicine ER -