Autophagy is required for the development and functionality of lacrimal gland-like organoids.
Kocak, Gamze Korsgen, Miriam E Amores, Leticia F Sun, Congxin Ceylan, Merve Ghazwani, Asmaa Kandirici, Merve Zatyka, Malgorzata Seranova, Elena Acharjee, Animesh
Kocak, Gamze
Korsgen, Miriam E
Amores, Leticia F
Sun, Congxin
Ceylan, Merve
Ghazwani, Asmaa
Kandirici, Merve
Zatyka, Malgorzata
Seranova, Elena
Acharjee, Animesh
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2025-12-18
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Abstract
Lacrimal glands (LGs) serve as pivotal exocrine glands crucial for protecting the ocular surface. Dysfunction in LG cell composition or secretion is implicated in dry eye disease (DED). While autophagy plays a vital role in tissue homeostasis in many organs, how it affects LG development and secretory function is not known. Here, we have undertaken a genetic study by utilizing autophagy-deficient human embryonic stem cells (hESCs) and differentiating them into LG-like organoids. Autophagy-deficient LG-like organoids exhibited improper development and secretion, along with increased protein aggregation, proliferation, and cell death. These phenotypes were associated with an accumulation of PAX6, a transcription factor crucial for brain and eye development, which we identified as an autophagy substrate. Pharmacological interventions with nicotinamide mononucleotide (NMN) and melatonin were able to rescue the cellular dysfunction in autophagy-deficient LG-like organoids. Together, our study highlights the role of autophagy in LG along with potential therapeutic interventions for DED.
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Kocak G, Korsgen ME, Amores LF, Sun C, Ceylan M, Ghazwani A, Kandirici M, Zatyka M, Seranova E, Acharjee A, Barrett T, Yuksel B, Mardinoglu A, Güven S, Sarkar S. Autophagy is required for the development and functionality of lacrimal gland-like organoids. Stem Cell Reports. 2026 Jan 13;21(1):102744. doi: 10.1016/j.stemcr.2025.102744.
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