|
| Animals | Cell injection(s) | Effects, longest time analyzed after injury | Distribution, longest time analyzed after transplantation | Mechanisms | References |
|
| Glaucoma models: rise of the intraocular pressure through several approaches, retinal ischemia/reperfusion |
|
| Adult female Wistar rats (MSCs were from male) | ivit rat BM-MSCs or rat AT-MSCs 1 w after injury
Dose: 200,000 cells | 4 w; RGCs retrogradely labeled, % to uninjured: BM-MSCs (83%); AT-MSCs (85%); untreated (65%) | 4 w; cells were integrated into GCL and INL | Reduced TNF-α and interferon-γ;
increased IL-1Ra and prostaglandin E2 receptor | [68] |
|
| Adult female Wistar rats | ivit rat BM-MSCs 2 w after injury
Dose: 200,000 cells | 4 w; RGCs retrogradely labeled, % to uninjured: BM-MSC (88%); untreated (80%) | 8 w; ILM, NFL, GCL | Increased expression of bFGF and CNTF | [69] |
|
| Adult brown Norway rats (sex not specified) | ivit BDNF-expressing rat BM-MSCs; rat BM-MSCs 2 d after injury
Dose: 200,000 cells | 6 w; BDNF-BM-MSCs treated animals had better pupil light reflex, ERG function, and optic nerve integrity; RGCs (Brn3a-positive cells) % to uninjured: BDNF-MSCs (56%); MSCs (29%) | 6 w; GCL, vitreous | Chronic low dose delivery of BDNF | [70] |
|
| Adult male Sprague-Dawley and Lewis rats |
ivit and IV rat live or dead BM-MSCs 1 w before the injury
Dose: 30,000 cells | 4 w; intravenous: no effect.
Intravitreal: RGCs survival (optic nerve damage): Lewis: 92% (live BM-MSC); 74% (dead BM-MSCs)
Sprague-Dawley: 89% (live BM-MSCs); 62% (dead BM-MSCs) | 5 w: majority of cells in the vitreous, few in the ILM, NFL, and GCL | n/a | [71] |
|
| Adult male Sprague-Dawley rats | ivit rat BM-MSCs
Dose: 180,000 | 4 w: RGCs (nuclei counting in the GCL): 1.3 fold increase to untreated | 4 w: vitreous, ILM, GCL | Increased expression of bFGF, CNTF, and BDNF | [72] |
|
| Aged male Sprague-Dawley rats | ivit BM-MSCs 6 w after injury
Dose: low (30,000 cells); high (100,000 cells) | 10 w: RGCs retrogradely labeled, % to uninjured: 40% (untreated), 58% (low dose); 69% (high dose)
Improved visual water box swimming test (better in high dose) | n/a | n/a | [73] |
|
| Adult brown Norway female rats | ant/cha murine BM-MSCs
Dose: 100,000 cells | 4 w: trabecular meshwork regeneration; decreased IOP; decreased RGCs degeneration (TUNEL+ cells) | 24 h: cells migrated to the damaged area 96 h: cells cleared | Secretion of paracrine factors; recruitment of ocular progenitor cells | [74] |
|
| Optic nerve crush or transection |
|
| Adult male and female Lister hooded rats | ivit rat BM-MNCs immediately after injury
Dose: 5,000,000 cells | 2 w: RGCs retrogradely labeled, % to uninjured: BM-MNCs (40%); vehicle (24%); higher optic nerve regeneration; 8 w: RGCs regeneration and reconnection to the superior colliculus | 2 w: very few cells GCL, INL, optic nerve | Müller glia modulation; bFGF, Tax1BP1, and SytIV increased expression | [34, 75, 76] |
|
| Adult male Sprague-Dawley rats | ivit rat BM-MSCs
Dose: low: 30,000; high: 100,000 | 2 w: higher optic nerve regeneration. High dose had more regeneration than low dose of BM-MSCs | n/a | n/a | [77] |
|
| Adult Wistar rats (sex not specified) | ivit NTF-secreting BM-MSCs; human BM-MSCs; rat BM-MSCs 3 d before the injury
Dose: 400,000 | 8 d: RGCs retrogradely labeled, % to uninjured: human NTF-BMSCs (69%); human BM-MSCs (66%); vehicle (46%); rat BM-MSCs had no neuroprotective effect | 24 d: vitreous | Neurotrophic factors secretion (GDNF, BDNF); possible inflammatory reaction to xenotransplantation | [33] |
|
| Adult male and female Lister hooded rats | ivit rat BM-MSCs
Dose: 500,000 | 4 w: RGCs (Tuj1+ and Brn3a+ cells; % to uninjured): 21% and 5% MSCs; 9% and 2% vehicle | 18 w: vitreous | Increased expression of bFGF and IL-1β | [35] |
|
| Adult male Sprague-Dawley rats | ivit rat DP-MSCs or rat BM-MSCs
Dose: 150,000 cells | 3 w: RGCs (β-III tub+ cells/mm): DP-MSCs (28), BM-MSCs (16), untreated (6.9); higher axon regeneration and RFNL thickness in both treated groups, best on DP-MSCs | 3 w: DP-MSCs in the vitreous; BM-MSCs n/a | Neurotrophic factors release (NGF, BDNF, and NT-3); DP-MSCs release more NGF and BDNF than BM-MSCs; reduced scar tissue on the crush site | [62] |
|
| In vitro: organotypical retinal explant culture |
|
| Adult Sprague-Dawley rats (sex not specified) | A droplet containing 1,000–5,000 BM-MSCs was placed on the RGCs surface | 1 w: RGCs number increased ~2-fold (Islet-1; NeuN, β-III tub); increased NFL and IPL thickness | 1 w: adjacent to GCL, not integrated into the retina | Secretion of growth factors, specially PDGF (also tested in vivo in a glaucoma model) | [61] |
|
