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Establishment, Maintenance, Differentiation, Genetic Manipulation, and Transplantation of Mouse and Human Lacrimal Gland Organoids
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Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.

Xinwei Jiao1, Xiaoting Pei1, Dingli Lu1

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|August 24, 2021
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Aging disrupts lacrimal glands, impacting gut microbiota and circadian rhythms. Fecal microbiota transplants (FMTs) from young donors rejuvenated gut bacteria and improved aging-related lacrimal gland dysfunction in old mice.

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Area of Science:

  • Ophthalmology
  • Gerontology
  • Microbiology

Background:

  • Lacrimal glands undergo age-related changes, but underlying mechanisms remain unclear.
  • Aging impacts gut microbiota and circadian rhythms, potentially affecting ocular health.
  • Age-associated lacrimal gland dysfunction presents a significant clinical challenge.

Purpose of the Study:

  • To investigate the interplay between aging, gut microbiota, and circadian rhythm in lacrimal gland dysfunction.
  • To determine if fecal microbiota transplantation (FMT) can ameliorate age-related lacrimal gland alterations.
  • To explore the molecular and structural changes in aging lacrimal glands.

Main Methods:

  • C57BL/6J mice were grouped into young, old, and old mice receiving FMT from young donors.
  • Gut microbial diversity was assessed using 16S rRNA sequencing.
  • Exorbital lacrimal gland (ELG) transcriptomic profiles were analyzed across a 24-hour circadian cycle using high-throughput sequencing.
  • Immunostaining evaluated lymphocytic infiltration, lipid deposition, and nerve innervation.

Main Results:

  • Old mice exhibited significant shifts in gut microbial communities compared to young mice.
  • Aging reprogrammed the circadian transcriptomic profile of ELGs.
  • FMT intervention restored gut microbial diversity and improved ELG rhythmic transcriptomic profiles.
  • FMT reduced chronic inflammation, lipid deposition, and aberrant neural responses in aging lacrimal glands.

Conclusions:

  • Age-associated gut dysbiosis contributes to lacrimal gland dysfunction.
  • Reconstitution of gut microbiota via FMT from young donors can improve aging-driven lacrimal gland circadian dysfunction.
  • Targeting the gut-lacrimal axis may offer therapeutic strategies for age-related dry eye disease.