nach oben

Documenta Ophthalmologica

Erschienen in:

10.02.2023 | Original Research Article

Rod photoreceptor activation and deactivation in early-stage diabetic eye disease

verfasst von: J. Jason McAnany, Jason C. Park

Erschienen in: Documenta Ophthalmologica | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To infer rod phototransduction activation and deactivation characteristics in diabetics who have mild or no clinically-apparent retinopathy.

Methods

Fifteen non-diabetic controls, 15 diabetics with no clinically-apparent diabetic retinopathy (NDR), and 15 diabetics with mild non-proliferative diabetic retinopathy (MDR) participated. Dark-adapted flash electroretinograms (3.2 to 4.4 log scot td-s) were recorded to assess rod activation. The a-waves were fit with a Gaussian model to derive R_mp3 (maximum photoreceptor response amplitude) and S (phototransduction sensitivity). Rod deactivation was assessed with a paired flash paradigm, in which a-waves were measured for two flashes separated by inter-stimulus intervals (ISIs) of 0.125 to 16 s. The ISI needed for the a-wave amplitude of the second flash to recover to 50% of the first flash (t₅₀) was determined. The effect of stimulus retinal illuminance on activation and deactivation was evaluated in a subset of control subjects.

Results

Analysis of variance indicated that both diabetic groups had significant log S reductions compared to controls (p < 0.001). Mean S was reduced by approximately 49% and 78% for the NDR and MDR groups, respectively. In contrast, log R_mp3 and log t₅₀ did not differ significantly among the groups (both p > 0.08). Reducing stimulus retinal illuminance significantly reduced S, but did not significantly affect R_max or t₅₀.

Conclusions

Only phototransduction sensitivity was abnormal in this sample of diabetic subjects. The normal deactivation kinetics suggests that circulating rod current is normal. These findings begin to constrain possible explanations for abnormal rod function in early diabetic retinal disease.

Nur mit Berechtigung zugänglich

Barber AJ (2003) A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 27(2):283–290. https://doi.org/10.1016/S0278-5846(03)00023-XCrossRefPubMed

Barber AJ, Baccouche B (2017) Neurodegeneration in diabetic retinopathy: potential for novel therapies. Vision Res 139:82–92. https://doi.org/10.1016/j.visres.2017.06.014CrossRefPubMed

Lieth E, Gardner TW, Barber AJ, Antonetti DA, Penn State Retina Research G (2000) Retinal neurodegeneration: early pathology in diabetes. Clin Exp Ophthalmol 28(1):3–8CrossRefPubMed

Lynch SK, Abramoff MD (2017) Diabetic retinopathy is a neurodegenerative disorder. Vision Res 139:101–107. https://doi.org/10.1016/j.visres.2017.03.003CrossRefPubMedPubMedCentral

Sohn EH, van Dijk HW, Jiao C, Kok PH, Jeong W, Demirkaya N, Garmager A, Wit F, Kucukevcilioglu M, van Velthoven ME, DeVries JH, Mullins RF, Kuehn MH, Schlingemann RO, Sonka M, Verbraak FD, Abramoff MD (2016) Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A 113(19):E2655-2664. https://doi.org/10.1073/pnas.1522014113CrossRefPubMedPubMedCentral

Elsner AE, Burns SA, Lobes LA Jr, Doft BH (1987) Cone photopigment bleaching abnormalities in diabetes. Invest Ophthalmol Vis Sci 28(4):718–724PubMed

Holopigian K, Greenstein VC, Seiple W, Hood DC, Carr RE (1997) Evidence for photoreceptor changes in patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 38(11):2355–2365PubMed

Kern TS (2017) Do photoreceptor cells cause the development of retinal vascular disease? Vision Res 139:65–71. https://doi.org/10.1016/j.visres.2017.03.011CrossRefPubMedPubMedCentral

Kern TS, Berkowitz BA (2015) Photoreceptors in diabetic retinopathy. J Diabetes Investig 6(4):371–380. https://doi.org/10.1111/jdi.12312CrossRefPubMedPubMedCentral

10.

Hood DC, Birch DG (1994) Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a-wave. Invest Ophthalmol Vis Sci 35(7):2948–2961PubMed

11.

Hood DC, Birch DG (1995) Phototransduction in human cones measured using the alpha-wave of the ERG. Vision Res 35(20):2801–2810CrossRefPubMed

12.

McAnany JJ, Park JC (2019) Cone photoreceptor dysfunction in early-stage diabetic retinopathy: Association between the activation phase of cone phototransduction and the flicker electroretinogram. Invest Ophthalmol Vis Sci 60(1):64–72. https://doi.org/10.1167/iovs.18-25946CrossRefPubMedPubMedCentral

13.

Birch DG, Hood DC, Nusinowitz S, Pepperberg DR (1995) Abnormal activation and inactivation mechanisms of rod transduction in patients with autosomal dominant retinitis pigmentosa and the pro-23-his mutation. Invest Ophthalmol Vis Sci 36(8):1603–1614PubMed

14.

Pepperberg DR, Birch DG, Hofmann KP, Hood DC (1996) Recovery kinetics of human rod phototransduction inferred from the two-branched alpha-wave saturation function. J Opt Soc Am A Opt Image Sci Vis 13(3):586–600. https://doi.org/10.1364/josaa.13.000586CrossRefPubMed

15.

Pepperberg DR, Birch DG, Hood DC (1997) Photoresponses of human rods in vivo derived from paired-flash electroretinograms. Vis Neurosci 14(1):73–82. https://doi.org/10.1017/s0952523800008774CrossRefPubMed

16.

Pepperberg DR, Birch DG, Hood DC (2000) Electroretinographic determination of human rod flash response in vivo. Methods Enzymol 316:202–223. https://doi.org/10.1016/s0076-6879(00)16725-4CrossRefPubMedPubMedCentral

17.

Arshavsky VY (2002) Rhodopsin phosphorylation: from terminating single photon responses to photoreceptor dark adaptation. Trends Neurosci 25(3):124–126. https://doi.org/10.1016/s0166-2236(00)02094-4CrossRefPubMed

18.

Burns ME, Baylor DA (2001) Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 24:779–805. https://doi.org/10.1146/annurev.neuro.24.1.779CrossRefPubMed

19.

Phipps JA, Yee P, Fletcher EL, Vingrys AJ (2006) Rod photoreceptor dysfunction in diabetes: activation, deactivation, and dark adaptation. Invest Ophthalmol Vis Sci 47(7):3187–3194. https://doi.org/10.1167/iovs.05-1493CrossRefPubMed

20.

Hansen RM, Harris ME, Moskowitz A, Fulton AB (2010) Deactivation of the rod response in retinopathy of prematurity. Doc Ophthalmol 121(1):29–35. https://doi.org/10.1007/s10633-010-9228-zCrossRefPubMedPubMedCentral

21.

Kang Derwent JJ, Derlacki DJ, Hetling JR, Fishman GA, Birch DG, Grover S, Stone EM, Pepperberg DR (2004) Dark adaptation of rod photoreceptors in normal subjects, and in patients with Stargardt disease and an ABCA4 mutation. Invest Ophthalmol Vis Sci 45(7):2447–2456. https://doi.org/10.1167/iovs.03-1178CrossRefPubMed

22.

Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM, Chew EY, Ferris FL 3rd, Knatterud GL (1998) Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early treatment diabetic retinopathy study report #18. Invest Ophthalmol Vis Sci 39(2):233–252PubMed

23.

McAnany JJ, Park JC, Chau FY, Leiderman YI, Lim JI, Blair NP (2018) Amplitude loss of the high-frequency flicker electroretinogram in early diabetic retinopathy. Retina. https://doi.org/10.1097/IAE.0000000000002262CrossRef

24.

Alexander KR, Rajagopalan AS, Raghuram A, Fishman GA (2006) Activation phase of cone phototransduction and the flicker electroretinogram in retinitis pigmentosa. Vision Res 46(17):2773–2785. https://doi.org/10.1016/j.visres.2006.01.007CrossRefPubMed

25.

Tzekov RT, Locke KG, Hood DC, Birch DG (2003) Cone and rod ERG phototransduction parameters in retinitis pigmentosa. Invest Ophthalmol Vis Sci 44(9):3993–4000CrossRefPubMed

26.

Hood DC, Birch DG (1993) Light adaptation of human rod receptors: the leading edge of the human a-wave and models of rod receptor activity. Vision Res 33(12):1605–1618CrossRefPubMed

27.

Robson JG, Frishman LJ (2014) The rod-driven a-wave of the dark-adapted mammalian electroretinogram. Prog Retin Eye Res 39:1–22. https://doi.org/10.1016/j.preteyeres.2013.12.003CrossRefPubMed

28.

McAnany JJ, Persidina OS, Park JC (2021) Clinical electroretinography in diabetic retinopathy: a review. Surv Ophthalmol. https://doi.org/10.1016/j.survophthal.2021.08.011CrossRefPubMedPubMedCentral

29.

Tzekov R, Arden GB (1999) The electroretinogram in diabetic retinopathy. Surv Ophthalmol 44(1):53–60CrossRefPubMed

30.

McAnany JJ, Liu K, Park JC (2020) Electrophysiological measures of dysfunction in early-stage diabetic retinopathy: No correlation between cone phototransduction and oscillatory potential abnormalities. Doc Ophthalmol 140(1):31–42. https://doi.org/10.1007/s10633-019-09718-2CrossRefPubMed

31.

Johnson MA, Hood DC (1996) Rod photoreceptor transduction is affected in central retinal vein occlusion associated with iris neovascularization. J Opt Soc Am A Opt Image Sci Vis 13(3):572–576. https://doi.org/10.1364/josaa.13.000572CrossRefPubMed

32.

Rahimi M, Leahy S, Blair NP, Shahidi M (2021) Variability of retinal oxygen metrics in healthy and diabetic subjects. Transl Vis Sci Technol 10(12):20. https://doi.org/10.1167/tvst.10.12.20CrossRefPubMedPubMedCentral

33.

Pechauer AD, Hwang TS, Hagag AM, Liu L, Tan O, Zhang X, Parker M, Huang D, Wilson DJ, Jia Y (2018) Assessing total retinal blood flow in diabetic retinopathy using multiplane en face Doppler optical coherence tomography. Br J Ophthalmol 102(1):126–130. https://doi.org/10.1136/bjophthalmol-2016-310042CrossRefPubMed

34.

Lorenzi M, Feke GT, Cagliero E, Pitler L, Schaumberg DA, Berisha F, Nathan DM, McMeel JW (2008) Retinal haemodynamics in individuals with well-controlled type 1 diabetes. Diabetologia 51(2):361–364. https://doi.org/10.1007/s00125-007-0872-0CrossRefPubMed

35.

Nippert AR, Newman EA (2020) Regulation of blood flow in diabetic retinopathy. Vis Neurosci 37:E004. https://doi.org/10.1017/S0952523820000036CrossRefPubMed

36.

Hafner J, Ginner L, Karst S, Leitgeb R, Unterluggauer M, Sacu S, Mitsch C, Scholda C, Pablik E, Schmidt-Erfurth U (2017) Regional patterns of retinal oxygen saturation and microvascular hemodynamic parameters preceding retinopathy in patients with type II diabetes. Invest Ophthalmol Vis Sci 58(12):5541–5547. https://doi.org/10.1167/iovs.17-22523CrossRefPubMed

37.

Cheung CY, Ikram MK, Klein R, Wong TY (2015) The clinical implications of recent studies on the structure and function of the retinal microvasculature in diabetes. Diabetologia 58(5):871–885. https://doi.org/10.1007/s00125-015-3511-1CrossRefPubMed

38.

Hardarson SH, Stefansson E (2012) Retinal oxygen saturation is altered in diabetic retinopathy. Br J Ophthalmol 96(4):560–563. https://doi.org/10.1136/bjophthalmol-2011-300640CrossRefPubMed

39.

Brigell M, Jeffrey BG, Mahroo OA, Tzekov R (2020) ISCEV extended protocol for derivation and analysis of the strong flash rod-isolated ERG a-wave. Doc Ophthalmol 140(1):5–12. https://doi.org/10.1007/s10633-019-09740-4CrossRefPubMed

40.

Henson DB, North RV (1979) Dark adaptation in diabetes mellitus. Br J Ophthalmol 63(8):539–541CrossRefPubMedPubMedCentral

41.

Jiang X, Mahroo OA (2022) Human retinal dark adaptation tracked in vivo with the electroretinogram: insights into processes underlying recovery of cone- and rod-mediated vision. J Physiol 600(21):4603–4621. https://doi.org/10.1113/JP283105CrossRefPubMed

42.

Hansen RM, Fulton AB (2005) Recovery of the rod photoresponse in infants. Invest Ophthalmol Vis Sci 46(2):764–768. https://doi.org/10.1167/iovs.04-0257CrossRefPubMed

43.

Phipps JA, Fletcher EL, Vingrys AJ (2004) Paired-flash identification of rod and cone dysfunction in the diabetic rat. Invest Ophthalmol Vis Sci 45(12):4592–4600. https://doi.org/10.1167/iovs.04-0842CrossRefPubMed

Titel: Rod photoreceptor activation and deactivation in early-stage diabetic eye disease
verfasst von: J. Jason McAnany
Jason C. Park
Publikationsdatum: 10.02.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Documenta Ophthalmologica / Ausgabe 3/2023
Print ISSN: 0012-4486
Elektronische ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-023-09925-y

Neu im Fachgebiet Augenheilkunde

Metastase in der periokulären Region

Metastasen Leitthema

Orbitale und periokuläre metastatische Tumoren galten früher als sehr selten. Aber mit der ständigen Aktualisierung von Medikamenten und Nachweismethoden für die Krebsbehandlung werden neue Chemotherapien und Strahlenbehandlungen eingesetzt. Die …

Staging und Systemtherapie bei okulären und periokulären Metastasen

Metastasen Leitthema

Metastasen bösartiger Erkrankungen sind die häufigsten Tumoren, die im Auge diagnostiziert werden. Sie treten bei ungefähr 5–10 % der Patienten mit soliden Tumoren im Verlauf der Erkrankung auf. Besonders häufig sind diese beim Mammakarzinom und …

Wundheilung nach Trabekulektomie

Trabekulektomie CME-Artikel

Die überschießende Wundheilung in der filtrierenden Glaukomchirurgie ist ein zentraler Faktor für ein operatives Versagen. Nach der Einführung der Trabekulektomie in den 1960er-Jahren wurden viele Faktoren erkannt, die mit einer vermehrten …

„standard operating procedures“ (SOP) – Vorschlag zum therapeutischen Management bei periokulären sowie intraokulären Metastasen

Metastasen Leitthema

Peri- sowie intraokuläre Metastasen sind insgesamt gesehen selten und meist Zeichen einer fortgeschrittenen primären Tumorerkrankung. Die Therapie ist daher zumeist palliativ und selten kurativ. Zudem ist die Therapiefindung sehr individuell. Die …

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2023

Electroretinographic abnormalities in Alport syndrome with a novel COL4A5 truncated variant (p.Try20GlyfsTer19)

Retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter’s syndrome

Evaluation of correlation between Diopsys® NOVA™ fixed-luminance flicker ERG and Diagnosys® Espion 2™ flicker ERG parameters

Phenotypic variability in PRPH2 as demonstrated by a family with incomplete penetrance of autosomal dominant cone-rod dystrophy

Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging

Frequency-domain analysis of transient visual evoked potentials in schizophrenia

Neu im Fachgebiet Augenheilkunde

Metastase in der periokulären Region

Staging und Systemtherapie bei okulären und periokulären Metastasen

Wundheilung nach Trabekulektomie

„standard operating procedures“ (SOP) – Vorschlag zum therapeutischen Management bei periokulären sowie intraokulären Metastasen

Update Augenheilkunde