Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy

Richert, Elisabeth; Koinzer, Stefan; Tode, Jan; Schlott, Kerstin; Brinkmann, Ralf; Hillenkamp, Jost; Klettner, Alexa; Roider, Johann

doi:10.1167/iovs.17-23163

Cited by 36 publications

(53 citation statements)

References 39 publications

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“…Some of these enlarged cells showed two nuclei (arrow), which suggest mitosis nificantly lower levels after SRT than in LPC [43]. It has also been shown that matrix metalloproteinases (MMPs), particularly the active form of MMP-2 is significantly upregulated [39,40,44] and also locally resolved as shown in Fig. 11.5 [39], which is assumed to play a positive role in preventing matrix degradation of Bruch's membrane, and eventually increasing transmembrane molecular exchange.…”

Section: Resultsmentioning

confidence: 94%

“…Cytokine release from RPE also alters after irradiation; an investigation with ex vivo RPE showed a decrease of the VEGF and an increase of the PEDF secretion from RPE cells 3 days after irradiation [39]. Proinflammatory cytokines, including IL-1β and TNF-α, showed siga b Fig.…”

Section: Resultsmentioning

confidence: 98%

“…Proinflammatory cytokines, including IL-1β and TNF-α, showed siga b Fig. 11.4 RPE porcine explants irradiated with 140 mJ/ cm 2 per pulse stained with the vitality marker Calcein AM showing vital cells with green fluorescence [39]. Immediately after treatment the square laser beam profile is visible (a).…”

Section: Resultsmentioning

confidence: 99%

“…Histology and electron microscopy collected at different points in time after irradiation of rabbit eyes display disrupted RPE cells without damage of surrounding tissues [38], thus confirming the selectivity of RPE damage. Depending on the site, the wound is completely recovered with RPE cells within less than 1 week [39,40] as shown in Fig. 11.4.…”

Section: Resultsmentioning

confidence: 99%

“…It has also been shown that matrix metalloproteinases (MMPs), particularly the active form of MMP-2 is significantly upregulated [39,40,44] and also locally resolved as shown in Fig. 11.5 [39], which is assumed to play a positive role in preventing matrix degradation of Bruch's membrane, and eventually increasing transmembrane molecular exchange. Human donor samples of Bruch's membranes incubated with MMP-2 showed considerably improved hydraulic conductivity and transport capabilities [17,40].…”

Section: Resultsmentioning

confidence: 99%

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Selective Retina Therapy

Považay

Brinkmann

Stoller³

et al. 2019

High Resolution Imaging in Microscopy and Ophthalmology

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Selective Retina Therapy

Považay

Brinkmann

Stoller³

et al. 2019

High Resolution Imaging in Microscopy and Ophthalmology

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Response of Retinal Pigment Epithelium (RPE)‐Choroid Explants to Thermal Stimulation Therapy of the RPE (TSR)

et al. 2020

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Background and Objectives: The thermal stimulation therapy of the retinal pigment epithelium (TSR) is a sublethal laser technique for thermal stimulation of the retinal pigment epithelium (RPE)-Bruch's membrane (BrM)-complex. The aim of this study was to investigate the influence of TSR on the release of age-related macular degeneration (AMD)-relevant cell mediators. Study Design/Materials and Methods: Porcine RPE-BrM-choroid explants were irradiated with a 532 nm continuous wave laser using different spot sizes (100-300 µm, duration 100 milliseconds, 15-100 mW). Cell death was investigated by calcein staining. Explants were treated with grids of sublethal spots and cultivated in modified Ussing chambers. The effect on matrix metalloproteinase-2 (MMP-2) and-9 was investigated by zymography and quantitative reverse transcription polymerase chain reaction. Secretion of vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), and transforming growth factor-β (TGF-β) was analyzed by enzyme-linked immunosorbent assay and expression of HSP70 was examined by western blot. Integrity of the RPE/BrM-complex was analyzed by scanning electron microscopy. Results: Laser powers of 15 mW (100 µm) and 45 mW (300 µm) did not induce RPE cell death. The integrity of the RPE/BrM-complex was not impaired after TSR. After TSR with 300 µm spot size, we observed a significant increase of active MMP-2 in the basal compartments. The content of PEDF significantly increased in treated explants in both compartments with 100 and 300 µm spot sizes. VEGF and TGF-β secretion was not triggered by TSR. Conclusions: TSR represents a possible RPE stimulating treatment for dry AMD. TSR increases the basal release of active MMP-2, which might reverse age-related thickening of BrM. VEGF secretion was not triggered by TSR while anti-angiogenic PEDF was increased, indicating an induction of an anti-angiogenic and neuroprotective environment. Lasers Surg. Med.

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One‐Year Functional and Anatomical Outcomes After Selective Retina Therapy With Real‐Time Feedback‐Controlled Dosimetry in Patients With Intermediate Age‐Related Macular Degeneration: A Pilot Study

2020

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Background and Objectives This pilot study sought to evaluate changes in macular function and drusen volume (DV) after selective retina therapy (SRT) in patients with intermediate age‐related macular degeneration (iAMD). Study Design/Materials and Methods Twenty participants with bilateral iAMD were included in this prospective interventional case series study. After titrating pulse energy by real‐time feedback‐controlled dosimetry, SRT with a wavelength of 527 nm was applied around the macula of one eye of each patient. Changes in best‐corrected visual acuity (BCVA), DV within the central 5‐mm ring (C5), and retinal sensitivity (RS) of the SRT‐treated eyes (treated eyes) and untreated fellow eyes (untreated eyes) were evaluated at baseline and then at 3, 6, 9, and 12 months after treatment using linear mixed models. Results The mean BCVA did not change significantly between baseline and 12 months in both treated and untreated eyes (P = 0.06, P = 0.24, respectively), whereas the BCVA increase rate was faster for treated than for untreated eyes at the 12‐month visit (–0.072 logMAR; 95% confidence interval [CI], −0.085 to −0.059 logMAR; P = 0.006). The mean cube root transformation of DV (cube root DV) within C5 in the untreated eyes increased significantly from 0.278 ± 0.115 at baseline to 0.295 ± 0.132 mm (P = 0.027) at 12 months, whereas the cube root DV change in treated eyes was not significant (P = 0.553). The rate of increase in the cube root DV was lower in treated than in untreated eyes at the 12‐month visit (−0.016 mm; 95% CI, −0.018 to −0.011 mm; P = 0.015). The mean RS was increased from 22.49 ± 2.40 dB to 24.09 ± 2.19 dB (P < 0.001) in the treated eyes, whereas the change of mean RS in the untreated eyes was not significant at the 12‐month visit (P = 0.18). The treated eyes had a higher rate of increase in RS than untreated eyes at the 12‐month visit (1.012 dB; 95% CI, 0.776–1.251 dB; P = 0.037). The RS change was significantly associated with the interaction between SRT treatment and time (P = 0.028), whereas it was not associated with cube root DV change (P = 0.106). No SRT‐related adverse effects were observed in all participants during the 1‐year follow‐up. Conclusion Since SRT improved the mean RS and reduced the rate of change in drusen load in the treated eyes, as compared to the untreated eyes, SRT might slow the progression of iAMD. However, further large randomized clinical trials are necessary to confirm the efficacy of SRT for iAMD. Lasers Surg. Med. © 2020 Wiley Periodicals LLC

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Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy

Abstract: SRT induces a cytokine profile, which may improve the flux across Bruch's membrane, slows down progression of early AMD by RPE regeneration, and inhibits the formation of choroidal neovascularization. The cytokine release depends on the size and density of applied laser spots.

Cited by 36 publications

References 39 publications

Selective Retina Therapy

Selective Retina Therapy

Response of Retinal Pigment Epithelium (RPE)‐Choroid Explants to Thermal Stimulation Therapy of the RPE (TSR)

One‐Year Functional and Anatomical Outcomes After Selective Retina Therapy With Real‐Time Feedback‐Controlled Dosimetry in Patients With Intermediate Age‐Related Macular Degeneration: A Pilot Study

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