Age-Related Changes in bis-Retinoids of Lipofuscin Granules in Human Retinal Pigment Epithelium Cells

---

Marina A. Yakovleva^1,2, Alexey A. Kostyukov¹, Natalya L. Aronshtam¹, Patimat M. Shilkrot³, Sergei A. Borzenok⁴, Vladimir A. Kuzmin¹, Tatiana B. Feldman^1,2,a*, Aleksandr E. Dontsov¹, and Mikhail A. Ostrovsky^1,2

¹Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia

²Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

³Dagestan Eye Microsurgery Center, 368305 Kaspiysk, Republic of Dagestan, Russia

⁴Svyatoslav Fyodorov Eye Microsurgery Complex, Ministry of Health of the Russian Federation, 127486 Moscow, Russia

^* To whom correspondence should be addressed.

Received: March 29, 2026; Revised: May 25, 2026; Accepted: May 25, 2026

---

Lipofuscin granules (LGs) in retinal pigment epithelium (RPE) cells contain bis-retinoids and their oxidation and degradation products, rendering them photo- and cytotoxic to intracellular structures. LGs are implicated in the pathogenesis of multiple visual pathologies, including age-related macular degeneration (AMD). They exhibit strong autofluorescence, which has led to the development of fundus autofluorescence (FAF) imaging as a non-invasive diagnostic method in ophthalmology. Spectral analysis of autofluorescence can expand the capabilities of this method, including for preclinical diagnostics, as pathological conditions are often associated with increased proportions of oxidized bis-retinoid derivatives that alter LG autofluorescence parameters. However, limited knowledge of age-dependent changes in LG bis-retinoid composition remains a key limitation. In this study, we combined fluorescence spectroscopy, confocal fluorescence microscopy, and fluorescence lifetime imaging (time-correlated single-photon counting) to demonstrate that, under physiological conditions, aging is accompanied by a progressive increase in the relative abundance of oxidation and degradation products of bis-retinoids in LGs. These findings provide an age-dependent baseline for distinguishing physiological and pathological states, thereby improving the potential of FAF imaging for early (preclinical) diagnosis.

---

KEY WORDS: eye, retinal pigment epithelium, lipofuscin granules, bis-retinoids, autofluorescence

DOI: 10.1134/S0006297926600985

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---