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. Author manuscript; available in PMC: 2025 Jun 1.
Published in final edited form as: Surv Ophthalmol. 2025 Jan 14;70(3):499–515. doi: 10.1016/j.survophthal.2025.01.003

Table 3. Articles on the outcomes of exosome treatment on the tear film of DED animal models.

Study Experimental target Source of
exosomes		 Exosome
volume		 Exosome
size		 Exosome delivery
method		 Exosome
content/
markers		 Outcomes measured Results
Yu et al. 2020 Mice subject to 5 days of desiccating stress exposure Human adipose tissue MSCs NA 100 nm Topically 4 times to murine cornea, after being labelled with PKH67 TSG101,
CD63, ALIX		 Fluorescein staining, tear production and PAS staining CFS decreased to 5.2 (+/- 0.84) from 12.0 (+/−2.44). Tear production improved from 2.40 + /− 0.49, to 6.10 + /−0.75. increased PAS-stained goblet cells
Wang et al.
2022		 BAC model of Male C57BL/6 mice (sham, PBS, positive control, 12.5, 25 and 50 mg/mL mADSC-
Exos)		 Mouse adipose derived mesenchymal stem cell exosomes (mADSC-Exos) 12.5, 25 and
50 mg/mL		 40-600 nm, average 134 nm 5 μL topically 3 times a day for 7 days CD9, CD63,
CD81		 Corneal fluoresceine staining, tear secretion, tear BUT TUNEL, Flow cytometry, qRT-PCR, Western blotting for corneal cytokines Increased tear volume (2.2 mL), increased TBUT (2.3 s) in the 50 mg/mL exos group, reduced corneal cell apoptosis, decreased levels of IL−1β, IL−6, IL−1α, caspase−1, IL-18, IFN-γ and TNF-α, increased levels of IL−10, and downregulation of NLRP3 inflammasome
Li et al. 2022 Adult female white rabbits with autoimmune dacryoadenitis-PBS group (n = 9) and exosome group (n = 9). Human umbilical cord MSCs NA 50−150 nm Subconjunctival injection of 30μg on days 1,3,5,7 and 9 after adoptive transfer of lymphocytes CD81, CD9,
CD63,
TSG101		 TBUT, corneal fluoresceine staining, tear volume, histopathological assessment of lacrimal gland and conjunctiva was performed at 8 weeks Improved CFS (9 vs 12), tear secretion (6 vs 4 mm), TBUT (7 vs 4 s); reduced lymphocytes in the lacrimal glands; reduced M1 macrophage markers (NOS2, IRF5, TNF-a, IL−1b and IL−6) and increased M2 macrophage markers (Arg1, CD206, KLF4, IL-10, TGF-b).
Guo et al. 2022 Female C57BL/6 mice, 3 groups with 4 mice per group; control, PBS and exosome groups Human umbilical cord MSCs 1μg/1μl 80−180 nm 1μl given topically
QID for 11 days		 CD9, CD63 and CD81 (Calnexin was negatively expressed) Tear volume, corneal fluorescein staining Improved tear production compared to PBS solution (2.7 vs 1.8 p = 0.0476). Reduced CFS;
Reduced mRNA expression of TNF-a, IL1b and IL−6 in the MSC-EV treated group.
Tian et al. 2023 C57BL mice, BAC model, the left eye served as control. 3 treatment groups 10 μL of PBS, MSC-Exo or MSC-Exo-Ce Murine bone marrow, Ce (NO3)3-6H2O was incorporated into the MSC-Exos to form The MSCExo-Ce 20−40μ/mL 100−150 nm Topical, 10μL of PBS, MSC-Exo, or MSCExo-Ce twice daily CD 48, CD
63, TSG101		 Tear production, fluorescein staining, ELISA of tear samples, histological assessment of cornea with H&E staining, in vivo ROS scavenging assay, distribution of MSC-Exo and MSC-Exo-Ce in vivo. Reduced CFS from 14 in to 1 (MSCExo-Ce), and 6 (MSC-Exo group). Improved epithelial integrity, central corneal thickness in the MSC-Exo-Ce group compared to MSC-Exo or PBS group.
Wang et al.
2023		 Female C57BL/6 mice aged 8−10 weeks subject to a desiccating environment and scopolamine administration. 8 groups (4 eyes per group); FML, PBS, control and 5 groups given varying concentrations of MSC-Exo of Human umbilical cord MSCs 0.5, 1.0, 2.0, 3.0 and 5.0 mg/mL Average
107.5 nm		 Topically 5pL given 4 times/day for 21 days CD9, CD63, CD81, Alix and calreticulin was negative Tear secretion, corneal fluorescein staining, cytokine profiles, TUNEL assay CFS decreased in all concentrations of exos (p < 0.05); improved tear volume in all groups; 3.0 mg/mL group had the lowest corneal fluorescein score (2.0 vs 9.3 p < 0.0001) and highest tear volume (3.5 vs 1.1 p < 0.001); decreased inflammatory cytokines in tears of exosomes group.
Ma et al. 2023 Divided into 5 groups of 6 mice each; control group with no BAC, saline group, mExo group, AA group, mExo@AA group. All groups treated with BAC, with 5 μL of 0.2% BAC twice/day for 7 days Mouse mesenchymal stem cell derived exosomes with and without ascorbic acid coupling 1 mg/mL 100−150 nm Topically twice/day for 7 days ALIX, beta-actin, TSG 101 positive, negative for GM130 Corneal fluorescein staining quantitative measurement, fluorescence DHE probe for ROS, CD206 fluorescence quantitative measurement, ELISA measurement of IL−6 and IL−1β in the tears, histological study of the cornea Less CFS with exo, saline and mExo@AA showed the least ROS with the DHE probe, Tears in the mExo@AA group had the lowest IL−6 and IL-1β, higher CD206, reduced corneal damage on histology. Tear production in mExo was 3.5 mm, mEXo-AA 5.5 mm, saline group 2 mm, control group 6.5 mm.

MSC − Mesenchymal Stromal Cell, PAS - Periodic acid-Schiff, CFS- Corneal Fluorescein Score, BAC − Benzalkonium Chloride, PBS − Phosphate Buffer Solution, TBUT − Tear Break Up Time, TUNEL - terminal deoxynucleotidyl transferase dUTP nick end labeling, qRT-PCR − Qualitative Reverse Transcription Polymerase Chain Reaction, ELISA - Enzyme-Linked Immunosorbent Assay, ROS- Reactive Oxygen Species, FML - Fluorometholone, AA- Ascorbic Acid, DHE − Dihydroethidium