Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
08
10
2019
accepted:
09
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
25
11
2020
Statut:
epublish
Résumé
We have developed a new technique to study the integrity, morphology and functionality of the retinal neurons and the retinal pigment epithelium (RPE). Young and old control albino (Sprague-Dawley) and pigmented (Piebald Virol Glaxo) rats, and dystrophic albino (P23H-1) and pigmented (Royal College of Surgeons) rats received a single intravitreal injection of 3% Fluorogold (FG) and their retinas were analyzed from 5 minutes to 30 days later. Retinas were imaged in vivo with SD-OCT and ex vivo in flat-mounts and in cross-sections. Fifteen minutes and 24 hours after intravitreal administration of FG retinal neurons and the RPE, but no glial cells, were labeled with FG-filled vesicles. The tracer reached the RPE 15 minutes after FG administration, and this labeling remained up to 30 days. Tracing for 15 minutes or 24 hours did not cause oxidative stress. Intraretinal tracing delineated the pathological retinal remodelling occurring in the dystrophic strains. The RPE of the P23H-1 strain was highly altered in aged animals, while the RPE of the RCS strain, which is unable to phagocytose, did not accumulate the tracer even at young ages when the retinal neural circuit is still preserved. In both dystrophic strains, the RPE cells were pleomorphic and polymegathic.
Identifiants
pubmed: 32350384
doi: 10.1038/s41598-020-64131-z
pii: 10.1038/s41598-020-64131-z
pmc: PMC7190639
doi:
Substances chimiques
2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
0
Stilbamidines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7273Références
Bonilha, V. L. Age and disease-related structural changes in the retinal pigment epithelium. Clin Ophthalmol 2, 413–424, https://doi.org/10.2147/opth.s2151 (2008).
doi: 10.2147/opth.s2151
pubmed: 19668732
pmcid: 2693982
Sparrow, J. R., Hicks, D. & Hamel, C. P. The retinal pigment epithelium in health and disease. Current molecular medicine 10, 802–823, https://doi.org/10.2174/156652410793937813 (2010).
doi: 10.2174/156652410793937813
pubmed: 21091424
Steinberg, R. H. Interactions between the retinal pigment epithelium and the neural retina. Documenta ophthalmologica. Advances in ophthalmology 60, 327–346, https://doi.org/10.1007/bf00158922 (1985).
doi: 10.1007/bf00158922
pubmed: 3905312
Strauss, O. The retinal pigment epithelium in visual function. Physiological reviews 85, 845–881, https://doi.org/10.1152/physrev.00021.2004 (2005).
doi: 10.1152/physrev.00021.2004
pubmed: 15987797
Jonas, J. B., Ohno-Matsui, K., Holbach, L. & Panda-Jonas, S. Retinal pigment epithelium cell density in relationship to axial length in human eyes. Acta ophthalmologica 95, e22–e28, https://doi.org/10.1111/aos.13188 (2017).
doi: 10.1111/aos.13188
pubmed: 27545271
Berman, E. R., Schwell, H. & Feeney, L. The retinal pigment epithelium. Chemical composition and structure. Investigative ophthalmology 13, 675–687 (1974).
pubmed: 4855060
Bhatia, S. K. et al. Analysis of RPE morphometry in human eyes. Molecular vision 22, 898–916 (2016).
pubmed: 27555739
pmcid: 4968610
Curcio, C. A., Zanzottera, E. C., Ach, T., Balaratnasingam, C. & Freund, K. B. Activated Retinal Pigment Epithelium, an Optical Coherence Tomography Biomarker for Progression in Age-Related Macular Degeneration. Investigative ophthalmology & visual science 58, BIO211–BIO226, https://doi.org/10.1167/iovs.17-21872 (2017).
doi: 10.1167/iovs.17-21872
Datta, S., Cano, M., Ebrahimi, K., Wang, L. & Handa, J. T. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Progress in retinal and eye research 60, 201–218, https://doi.org/10.1016/j.preteyeres.2017.03.002 (2017).
doi: 10.1016/j.preteyeres.2017.03.002
pubmed: 28336424
pmcid: 5600827
Gu, X. et al. Age-related changes in the retinal pigment epithelium (RPE). PloS one 7, e38673, https://doi.org/10.1371/journal.pone.0038673 (2012).
doi: 10.1371/journal.pone.0038673
pubmed: 22701690
pmcid: 3372495
Katz, M. L. & Robison, W. G. Jr. Age-related changes in the retinal pigment epithelium of pigmented rats. Experimental eye research 38, 137–151, https://doi.org/10.1016/0014-4835(84)90098-8 (1984).
doi: 10.1016/0014-4835(84)90098-8
pubmed: 6714331
Okubo, A. et al. The relationships of age changes in retinal pigment epithelium and Bruch’s membrane. Investigative ophthalmology & visual science 40, 443–449 (1999).
Fisher, C. R. & Ferrington, D. A. Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE. Investigative ophthalmology & visual science 59, AMD41–AMD47, https://doi.org/10.1167/iovs.18-24289 (2018).
doi: 10.1167/iovs.18-24289
Garcia-Layana, A., Cabrera-Lopez, F., Garcia-Arumi, J., Arias-Barquet, L. & Ruiz-Moreno, J. M. Early and intermediate age-related macular degeneration: update and clinical review. Clinical interventions in aging 12, 1579–1587, https://doi.org/10.2147/CIA.S142685 (2017).
doi: 10.2147/CIA.S142685
pubmed: 29042759
pmcid: 5633280
Osigian, C. J. et al. Retinal pigment epithelium changes in pediatric patients with glaucoma drainage devices. American journal of ophthalmology case reports 9, 23–27, https://doi.org/10.1016/j.ajoc.2017.12.001 (2018).
doi: 10.1016/j.ajoc.2017.12.001
pubmed: 29468212
Wang, X. N., Li, S. T., Li, W., Hua, Y. J. & Wu, Q. The thickness and volume of the choroid, outer retinal layers and retinal pigment epithelium layer changes in patients with diabetic retinopathy. International journal of ophthalmology 11, 1957–1962, https://doi.org/10.18240/ijo.2018.12.14 (2018).
doi: 10.18240/ijo.2018.12.14
pubmed: 30588430
pmcid: 6288528
Zhang, Q. et al. Comparison of histologic findings in age-related macular degeneration with RPE flatmount images. Molecular vision 25, 70–78 (2019).
pubmed: 30820143
pmcid: 6377373
Marc, R. E., Jones, B. W., Watt, C. B. & Strettoi, E. Neural remodeling in retinal degeneration. Progress in retinal and eye research 22, 607–655 (2003).
doi: 10.1016/S1350-9462(03)00039-9
Garcia-Ayuso, D. et al. Retinal ganglion cell numbers and delayed retinal ganglion cell death in the P23H rat retina. Experimental eye research 91, 800–810, https://doi.org/10.1016/j.exer.2010.10.003 (2010).
doi: 10.1016/j.exer.2010.10.003
pubmed: 20955700
Garcia-Ayuso, D. et al. Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration. Molecular vision 17, 1716–1733 (2011).
pubmed: 21738401
pmcid: 3130728
Garcia-Ayuso, D. et al. Sectorial loss of retinal ganglion cells in inherited photoreceptor degeneration is due to RGC death. The British journal of ophthalmology 98, 396–401, https://doi.org/10.1136/bjophthalmol-2013-303958 (2014).
doi: 10.1136/bjophthalmol-2013-303958
pubmed: 24326325
Milam, A. H., Li, Z. Y. & Fariss, R. N. Histopathology of the human retina in retinitis pigmentosa. Progress in retinal and eye research 17, 175–205 (1998).
doi: 10.1016/S1350-9462(97)00012-8
Villegas-Perez, M. P., Lawrence, J. M., Vidal-Sanz, M., Lavail, M. M. & Lund, R. D. Ganglion cell loss in RCS rat retina: a result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium. The Journal of comparative neurology 392, 58–77 (1998).
doi: 10.1002/(SICI)1096-9861(19980302)392:1<58::AID-CNE5>3.0.CO;2-O
Villegas-Perez, M. P., Vidal-Sanz, M. & Lund, R. D. Mechanism of retinal ganglion cell loss in inherited retinal dystrophy. Neuroreport 7, 1995–1999, https://doi.org/10.1097/00001756-199608120-00028 (1996).
doi: 10.1097/00001756-199608120-00028
pubmed: 8905711
Chew, M. C., Lim, L. W., Tan, E. & Tan, C. S. Comparability of retinal thickness measurements using different scanning protocols on spectral-domain optical coherence tomography. International ophthalmology 36, 791–797, https://doi.org/10.1007/s10792-016-0197-4 (2016).
doi: 10.1007/s10792-016-0197-4
pubmed: 26887565
Cuenca, N., Ortuno-Lizaran, I. & Pinilla, I. Cellular Characterization of OCT and Outer Retinal Bands Using Specific Immunohistochemistry Markers and Clinical Implications. Ophthalmology 125, 407–422, https://doi.org/10.1016/j.ophtha.2017.09.016 (2018).
doi: 10.1016/j.ophtha.2017.09.016
pubmed: 29037595
Ortin-Martinez, A. et al. A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF. PloS one 9, e113798, https://doi.org/10.1371/journal.pone.0113798 (2014).
doi: 10.1371/journal.pone.0113798
pubmed: 25464513
pmcid: 4252057
Panda-Jonas, S., Jonas, J. B. & Jakobczyk-Zmija, M. Retinal pigment epithelial cell count, distribution, and correlations in normal human eyes. American journal of ophthalmology 121, 181–189, https://doi.org/10.1016/s0002-9394(14)70583-5 (1996).
doi: 10.1016/s0002-9394(14)70583-5
pubmed: 8623888
Pinilla, I. et al. Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence. Experimental eye research 150, 122–134, https://doi.org/10.1016/j.exer.2015.10.012 (2016).
doi: 10.1016/j.exer.2015.10.012
pubmed: 26521765
Rovere, G. et al. Comparison of Retinal Nerve Fiber Layer Thinning and Retinal Ganglion Cell Loss After Optic Nerve Transection in Adult Albino Rats. Investigative ophthalmology & visual science 56, 4487–4498, https://doi.org/10.1167/iovs.15-17145 (2015).
doi: 10.1167/iovs.15-17145
Schmidt-Erfurth, U., Klimscha, S., Waldstein, S. M. & Bogunovic, H. A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration. Eye (Lond) 31, 26–44, https://doi.org/10.1038/eye.2016.227 (2017).
doi: 10.1038/eye.2016.227
Banda, H. K., Shah, G. K. & Blinder, K. J. Applications of fundus autofluorescence and widefield angiography in clinical practice. Canadian journal of ophthalmology. Journal canadien d’ophtalmologie 54, 11–19, https://doi.org/10.1016/j.jcjo.2018.10.003 (2019).
doi: 10.1016/j.jcjo.2018.10.003
pubmed: 30851762
Clemens, C. R. & Eter, N. Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring. Ophthalmologica. Journal international d’ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde 235, 1–9, https://doi.org/10.1159/000439445 (2016).
doi: 10.1159/000439445
pubmed: 26489018
Pichi, F., Abboud, E. B., Ghazi, N. G. & Khan, A. O. Fundus autofluorescence imaging in hereditary retinal diseases. Acta ophthalmologica 96, e549–e561, https://doi.org/10.1111/aos.13602 (2018).
doi: 10.1111/aos.13602
pubmed: 29098804
Schmitz-Valckenberg, S., Holz, F. G., Bird, A. C. & Spaide, R. F. Fundus autofluorescence imaging: review and perspectives. Retina 28, 385–409, https://doi.org/10.1097/IAE.0b013e318164a907 (2008).
doi: 10.1097/IAE.0b013e318164a907
pubmed: 18327131
Tsang, S. H. & Sharma, T. Fundus Autofluorescence. Advances in experimental medicine and biology 1085, 15–16, https://doi.org/10.1007/978-3-319-95046-4_4 (2018).
doi: 10.1007/978-3-319-95046-4_4
pubmed: 30578477
von Ruckmann, A., Fitzke, F. W. & Bird, A. C. Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. The British journal of ophthalmology 79, 407–412, https://doi.org/10.1136/bjo.79.5.407 (1995).
doi: 10.1136/bjo.79.5.407
Yung, M., Klufas, M. A. & Sarraf, D. Clinical applications of fundus autofluorescence in retinal disease. International journal of retina and vitreous 2, 12, https://doi.org/10.1186/s40942-016-0035-x (2016).
doi: 10.1186/s40942-016-0035-x
pubmed: 27847630
pmcid: 5088473
Lei, L. et al. Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell. International journal of molecular sciences 18, https://doi.org/10.3390/ijms18040728 (2017).
Sparrow, J. R., Yoon, K. D., Wu, Y. & Yamamoto, K. Interpretations of fundus autofluorescence from studies of the bisretinoids of the retina. Investigative ophthalmology & visual science 51, 4351–4357, https://doi.org/10.1167/iovs.10-5852 (2010).
doi: 10.1167/iovs.10-5852
Ly, A., Nivison-Smith, L., Assaad, N. & Kalloniatis, M. Fundus Autofluorescence in Age-related Macular Degeneration. Optometry and vision science: official publication of the American Academy of Optometry 94, 246–259, https://doi.org/10.1097/OPX.0000000000000997 (2017).
doi: 10.1097/OPX.0000000000000997
Spaide, R. F. & Curcio, C. A. Drusen characterization with multimodal imaging. Retina 30, 1441–1454, https://doi.org/10.1097/IAE.0b013e3181ee5ce8 (2010).
doi: 10.1097/IAE.0b013e3181ee5ce8
pubmed: 20924263
pmcid: 2952278
Georgiadis, A. et al. The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice. PloS one 5, e15730, https://doi.org/10.1371/journal.pone.0015730 (2010).
doi: 10.1371/journal.pone.0015730
pubmed: 21209887
pmcid: 3012699
Matsumoto, E. et al. Fabricating retinal pigment epithelial cell sheets derived from human induced pluripotent stem cells in an automated closed culture system for regenerative medicine. PloS one 14, e0212369, https://doi.org/10.1371/journal.pone.0212369 (2019).
doi: 10.1371/journal.pone.0212369
pubmed: 30865653
pmcid: 6415881
Obert, E. et al. Targeting the tight junction protein, zonula occludens-1, with the connexin43 mimetic peptide, alphaCT1, reduces VEGF-dependent RPE pathophysiology. J Mol Med (Berl) 95, 535–552, https://doi.org/10.1007/s00109-017-1506-8 (2017).
doi: 10.1007/s00109-017-1506-8
Zech, J. C. et al. Effect of cytokines and nitric oxide on tight junctions in cultured rat retinal pigment epithelium. Investigative ophthalmology & visual science 39, 1600–1608 (1998).
Farjood, F. & Vargis, E. Physical disruption of cell-cell contact induces VEGF expression in RPE cells. Molecular vision 23, 431–446 (2017).
pubmed: 28761317
pmcid: 5524271
Yang, X., Chung, J. Y., Rai, U. & Esumi, N. Cadherins in the retinal pigment epithelium (RPE) revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo. PloS one 13, e0191279, https://doi.org/10.1371/journal.pone.0191279 (2018).
doi: 10.1371/journal.pone.0191279
pubmed: 29338041
pmcid: 5770047
Schmued, L. C. & Fallon, J. H. Fluoro-Gold: a new fluorescent retrograde axonal tracer with numerous unique properties. Brain research 377, 147–154, https://doi.org/10.1016/0006-8993(86)91199-6 (1986).
doi: 10.1016/0006-8993(86)91199-6
pubmed: 2425899
Gomez-Ramirez, A. M. & Villegas-Perez, M. P. Miralles de Imperial, J., Salvador-Silva, M. & Vidal-Sanz, M. Effects of intramuscular injection of botulinum toxin and doxorubicin on the survival of abducens motoneurons. Investigative ophthalmology & visual science 40, 414–424 (1999).
Lanciego, J. L. & Wouterlood, F. G. A half century of experimental neuroanatomical tracing. Journal of chemical neuroanatomy 42, 157–183, https://doi.org/10.1016/j.jchemneu.2011.07.001 (2011).
doi: 10.1016/j.jchemneu.2011.07.001
pubmed: 21782932
Nadal-Nicolas, F. M. et al. Transient Downregulation of Melanopsin Expression After Retrograde Tracing or Optic Nerve Injury in Adult Rats. Investigative ophthalmology & visual science 56, 4309–4323, https://doi.org/10.1167/iovs.15-16963 (2015).
doi: 10.1167/iovs.15-16963
Selles-Navarro, I., Villegas-Perez, M. P., Salvador-Silva, M., Ruiz-Gomez, J. M. & Vidal-Sanz, M. Retinal ganglion cell death after different transient periods of pressure-induced ischemia and survival intervals. A quantitative in vivo study. Investigative ophthalmology & visual science 37, 2002–2014 (1996).
Kobbert, C. et al. Current concepts in neuroanatomical tracing. Progress in neurobiology 62, 327–351 (2000).
doi: 10.1016/S0301-0082(00)00019-8
Wessendorf, M. W. Fluoro-Gold: composition, and mechanism of uptake. Brain research 553, 135–148, https://doi.org/10.1016/0006-8993(91)90241-m (1991).
doi: 10.1016/0006-8993(91)90241-m
pubmed: 1933270
Di Pierdomenico, J. et al. Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration. Investigative ophthalmology & visual science 59, 4392–4403, https://doi.org/10.1167/iovs.18-24621 (2018).
doi: 10.1167/iovs.18-24621
Garcia-Ayuso, D. et al. Changes in the photoreceptor mosaic of P23H-1 rats during retinal degeneration: implications for rod-cone dependent survival. Investigative ophthalmology & visual science 54, 5888–5900, https://doi.org/10.1167/iovs.13-12643 (2013).
doi: 10.1167/iovs.13-12643
LaVail, M. M. et al. Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration. Experimental eye research 167, 56–90, https://doi.org/10.1016/j.exer.2017.10.023 (2018).
doi: 10.1016/j.exer.2017.10.023
pubmed: 29122605
Di Pierdomenico, J. et al. Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities. Frontiers in neuroanatomy 11, 14, https://doi.org/10.3389/fnana.2017.00014 (2017).
doi: 10.3389/fnana.2017.00014
pubmed: 28321183
pmcid: 5337514
LaVail, M. M. Photoreceptor characteristics in congenic strains of RCS rats. Investigative ophthalmology & visual science 20, 671–675 (1981).
Lopez, R. et al. Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. Investigative ophthalmology & visual science 30, 586–588 (1989).
Nadal-Nicolas, F. M., Vidal-Sanz, M. & Agudo-Barriuso, M. The aging rat retina: from function to anatomy. Neurobiology of aging 61, 146–168, https://doi.org/10.1016/j.neurobiolaging.2017.09.021 (2018).
doi: 10.1016/j.neurobiolaging.2017.09.021
pubmed: 29080498
Wang, S. et al. Evolving neurovascular relationships in the RCS rat with age. Current eye research 27, 183–196, https://doi.org/10.1076/ceyr.27.3.183.16053 (2003).
doi: 10.1076/ceyr.27.3.183.16053
pubmed: 14562184
Zambarakji, H. J. et al. High resolution imaging of fluorescein patterns in RCS rat retinae and their direct correlation with histology. Experimental eye research 82, 164–171, https://doi.org/10.1016/j.exer.2005.06.006 (2006).
doi: 10.1016/j.exer.2005.06.006
pubmed: 16054136
Garcia-Ayuso, D., Di Pierdomenico, J., Agudo-Barriuso, M., Vidal-Sanz, M. & Villegas-Perez, M. P. Retinal remodeling following photoreceptor degeneration causes retinal ganglion cell death. Neural regeneration research 13, 1885–1886, https://doi.org/10.4103/1673-5374.239436 (2018).
doi: 10.4103/1673-5374.239436
pubmed: 30233058
pmcid: 6183041
Garcia-Ayuso, D., Di Pierdomenico, J., Vidal-Sanz, M. & Villegas-Perez, M. P. Retinal Ganglion Cell Death as a Late Remodeling Effect of Photoreceptor Degeneration. International journal of molecular sciences 20, https://doi.org/10.3390/ijms20184649 (2019).
Nadal-Nicolas, F. M. et al. Microglial dynamics after axotomy-induced retinal ganglion cell death. Journal of neuroinflammation 14, 218, https://doi.org/10.1186/s12974-017-0982-7 (2017).
doi: 10.1186/s12974-017-0982-7
pubmed: 29121969
pmcid: 5679427
Murdaugh, L. S. et al. Compositional studies of human RPE lipofuscin. Journal of mass spectrometry: JMS 45, 1139–1147, https://doi.org/10.1002/jms.1795 (2010).
doi: 10.1002/jms.1795
pubmed: 20860013
Coscas, G. et al. SD-OCT pattern of retinal venous occlusion with cystoid macular edema treated with Ozurdex(R). European journal of ophthalmology 21, 631–636, https://doi.org/10.5301/EJO.2011.7428 (2011).
doi: 10.5301/EJO.2011.7428
pubmed: 21500185
Hwang, H. S., Chae, J. B., Kim, J. Y. & Kim, D. Y. Association Between Hyperreflective Dots on Spectral-Domain Optical Coherence Tomography in Macular Edema and Response to Treatment. Investigative ophthalmology & visual science 58, 5958–5967, https://doi.org/10.1167/iovs.17-22725 (2017).
doi: 10.1167/iovs.17-22725
Turgut, B. & Yildirim, H. The causes of hyperreflective dots in optical coherence tomography excluding diabetic macular edema and retinal venous occlusion section sign. The open ophthalmology journal 9, 36–40, https://doi.org/10.2174/1874364101509010036 (2015).
doi: 10.2174/1874364101509010036
pubmed: 25926902
pmcid: 4407005
Catapano, L. A., Magavi, S. S. & Macklis, J. D. Neuroanatomical tracing of neuronal projections with Fluoro-Gold. Methods Mol Biol 438, 353–359, https://doi.org/10.1007/978-1-59745-133-8_27 (2008).
doi: 10.1007/978-1-59745-133-8_27
pubmed: 18369770
Brown, E. E., DeWeerd, A. J., Ildefonso, C. J., Lewin, A. S. & Ash, J. D. Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors. Redox biology 24, 101201, https://doi.org/10.1016/j.redox.2019.101201 (2019).
doi: 10.1016/j.redox.2019.101201
pubmed: 31039480
pmcid: 6488819
Kim, G. H. et al. Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice. Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 254, 705–716, https://doi.org/10.1007/s00417-015-3258-x (2016).
doi: 10.1007/s00417-015-3258-x
pubmed: 26743754
Ko, M. K., Saraswathy, S., Parikh, J. G. & Rao, N. A. The role of TLR4 activation in photoreceptor mitochondrial oxidative stress. Investigative ophthalmology & visual science 52, 5824–5835, https://doi.org/10.1167/iovs.10-6357 (2011).
doi: 10.1167/iovs.10-6357
Zhang, Y. et al. Early AMD-like defects in the RPE and retinal degeneration in aged mice with RPE-specific deletion of Atg5 or Atg7. Molecular vision 23, 228–241 (2017).
doi: 10.1167/17.10.228
Smedowski, A. et al. FluoroGold-Labeled Organotypic Retinal Explant Culture for Neurotoxicity Screening Studies. Oxidative medicine and cellular longevity 2018, 2487473, https://doi.org/10.1155/2018/2487473 (2018).
doi: 10.1155/2018/2487473
pubmed: 29560079
pmcid: 5831603
Steinberg, R. H. et al. Transgenic rat models of inherited retinal degeneration caused by mutant opsin genes. Inves. Ophthalmol Vis Sci 37, S698 (1996).
Di Pierdomenico, J. et al. Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats. Investigative ophthalmology & visual science 57, 3533–3544, https://doi.org/10.1167/iovs.16-19618 (2016).
doi: 10.1167/iovs.16-19618
Vidal-Sanz, M. et al. Death and neuroprotection of retinal ganglion cells after different types of injury. Neurotoxicity research 2, 215–227 (2000).
doi: 10.1007/BF03033795
Nadal-Nicolas, F. M. et al. Whole number, distribution and co-expression of brn3 transcription factors in retinal ganglion cells of adult albino and pigmented rats. PloS one 7, e49830, https://doi.org/10.1371/journal.pone.0049830 (2012).
doi: 10.1371/journal.pone.0049830
pubmed: 23166779
pmcid: 3500320
Salinas-Navarro, M. et al. A computerized analysis of the entire retinal ganglion cell population and its spatial distribution in adult rats. Vision research 49, 115–126, https://doi.org/10.1016/j.visres.2008.09.029 (2009).
doi: 10.1016/j.visres.2008.09.029
pubmed: 18952118
Sonoda, S. et al. A protocol for the culture and differentiation of highly polarized human retinal pigment epithelial cells. Nature protocols 4, 662–673, https://doi.org/10.1038/nprot.2009.33 (2009).
doi: 10.1038/nprot.2009.33
pubmed: 19373231
pmcid: 2688697
Valiente-Soriano, F. J. et al. Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina. Frontiers in neuroanatomy 8, 131, https://doi.org/10.3389/fnana.2014.00131 (2014).
doi: 10.3389/fnana.2014.00131
pubmed: 25477787
pmcid: 4238377