Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy.
Age- related macular degeneration (AMD)
Regeneration
Rejuvenation
Selective retina therapy (SRT)
Thermal stimulation of the retina (TSR)
Journal
BMC ophthalmology
ISSN: 1471-2415
Titre abrégé: BMC Ophthalmol
Pays: England
ID NLM: 100967802
Informations de publication
Date de publication:
30 Nov 2021
30 Nov 2021
Historique:
received:
03
12
2020
accepted:
22
11
2021
entrez:
1
12
2021
pubmed:
2
12
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.
Sections du résumé
BACKGROUND
BACKGROUND
Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration.
METHODS
METHODS
For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation.
RESULTS
RESULTS
TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells.
CONCLUSIONS
CONCLUSIONS
SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.
Identifiants
pubmed: 34847865
doi: 10.1186/s12886-021-02188-8
pii: 10.1186/s12886-021-02188-8
pmc: PMC8630886
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
412Informations de copyright
© 2021. The Author(s).
Références
Lipids Health Dis. 2018 Jan 4;17(1):3
pubmed: 29301530
Invest Ophthalmol Vis Sci. 2011 Mar 28;52(3):1780-7
pubmed: 21087969
Nat Genet. 2016 Feb;48(2):134-43
pubmed: 26691988
Exp Eye Res. 2018 May;170:117-126
pubmed: 29454858
J Clin Med. 2021 May 29;10(11):
pubmed: 34072472
Invest Ophthalmol Vis Sci. 2002 Feb;43(2):458-65
pubmed: 11818391
Ophthalmology. 2019 Jun;126(6):829-838
pubmed: 30244144
Am J Ophthalmol Case Rep. 2020 Jun 23;19:100794
pubmed: 32637732
Nat Med. 2008 Feb;14(2):194-8
pubmed: 18223656
Graefes Arch Clin Exp Ophthalmol. 2021 Jun;259(6):1401-1410
pubmed: 33205239
Ophthalmologe. 2006 Sep;103(9):742-8
pubmed: 16924447
Transl Vis Sci Technol. 2018 May 1;7(3):2
pubmed: 29736323
PLoS One. 2011 Apr 29;6(4):e19456
pubmed: 21559389
Immunol Lett. 2012 Sep;147(1-2):29-33
pubmed: 22698681
BMC Public Health. 2015 Sep 03;15:855
pubmed: 26334523
Retina. 2014 Oct;34(10):2010-20
pubmed: 24837050
Clin Diagn Lab Immunol. 2001 Nov;8(6):1131-5
pubmed: 11687452
Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2035-42
pubmed: 10892840
Exp Eye Res. 2019 Apr;181:346-355
pubmed: 30292489
FASEB J. 2015 Feb;29(2):696-710
pubmed: 25392267
Clin Biochem. 2006 Mar;39(3):267-76
pubmed: 16409998
Methods Mol Biol. 2019;1834:109-118
pubmed: 30324440
J Pers Med. 2021 May 13;11(5):
pubmed: 34067994
Exp Eye Res. 2010 Jun;90(6):703-10
pubmed: 20206163
Invest Ophthalmol Vis Sci. 2011 Jun 01;52(6):3842-53
pubmed: 21330654
Retina. 2014 Jan;34(1):87-97
pubmed: 23873164
J Biomed Opt. 2012 Jun;17(6):061219
pubmed: 22734749
Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1323-1331
pubmed: 29625455
Clin Ophthalmol. 2020 Oct 01;14:2983-2993
pubmed: 33061284
Cytokine X. 2020 Jun 20;2(3):100031
pubmed: 33604557
J Biomed Opt. 2017 Nov;22(11):1-11
pubmed: 29164836
Arch Ophthalmol. 1992 Dec;110(12):1786-92
pubmed: 1463423
Transl Vis Sci Technol. 2019 Nov 13;8(6):11
pubmed: 31737435
Lasers Surg Med. 2021 Mar;53(3):359-369
pubmed: 32567146
Transl Vis Sci Technol. 2020 Apr 28;9(5):23
pubmed: 32821495
Graefes Arch Clin Exp Ophthalmol. 2017 Jul;255(7):1375-1383
pubmed: 28421342
Exp Eye Res. 2012 Apr;97(1):63-72
pubmed: 22387137
Adv Med Sci. 2020 Mar;65(1):71-77
pubmed: 31918066
Front Med (Lausanne). 2021 Jul 16;8:682264
pubmed: 34336888
Exp Eye Res. 2020 Nov;200:108214
pubmed: 32898511
Lasers Surg Med. 2021 Apr;53(4):499-513
pubmed: 32757324
Invest Ophthalmol Vis Sci. 1999 Feb;40(2):443-9
pubmed: 9950604
Br J Ophthalmol. 2011 Dec;95(12):1638-45
pubmed: 21890786
Graefes Arch Clin Exp Ophthalmol. 2010 Sep;248(9):1263-72
pubmed: 20393742
Graefes Arch Clin Exp Ophthalmol. 2009 Nov;247(11):1487-92
pubmed: 19603178
Am J Ophthalmol. 2002 Sep;134(3):411-31
pubmed: 12208254
N Engl J Med. 2011 May 19;364(20):1897-908
pubmed: 21526923
Ophthalmology. 1992 Jun;99(6):933-43
pubmed: 1630784
PLoS One. 2010 Apr 23;5(4):e10329
pubmed: 20428236
J Clin Med. 2020 Apr 09;9(4):
pubmed: 32283698
Clin Exp Ophthalmol. 2014 Jul;42(5):466-79
pubmed: 24118741
FASEB J. 2010 Dec;24(12):4816-24
pubmed: 20686107
J Cell Physiol. 2001 Dec;189(3):323-33
pubmed: 11748590
Am J Pathol. 1995 May;146(5):1029-39
pubmed: 7538264
Arch Ophthalmol. 1999 Aug;117(8):1028-34
pubmed: 10448745