Table 2.
In vivo studies on TUDCA effect in animals of retinal disorder.
|
Author,
Year (Country) |
Theme |
Animals
(Sex and Old) |
Models |
Sample
Size(n) |
TUDCA Route and Dose | Frequency and Duration |
Follow
Up |
Tissues | Laboratory Techniques | Major Findings |
|---|---|---|---|---|---|---|---|---|---|---|
| M.Joe Phillips, 2008 (USA, Korea) [57] | RP | Rd10 mice (sex not specified, neonatal) | Rd10 mutant mice | n = 17 or n = 14 per group | Subcutaneous injections (500 mg/kg body weight) | Once every 3 days, P6-P30, 8 times total | P30 | Eye ball | ERG, immunolabeling, TUNEL staining | Preserve rod and cone function and overall photoreceptor numbers, reduction of apoptosis in RP model |
| Laura Fernández-Sánchez, 2011 (Spain) [58] | RP | P23H rats (sex not specified, neonatal) | P23H mutant rats | n = 18-22 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a week, P21-P120 |
P120 | Eye ball | ERG, IHC, TUNEL staining | Preserve cone and rod structure and function, together with their contacts with their postsynaptic neurons, reduction of apoptosis in the RP model |
| Brian C. Oveson, 2011 (USA) [59] | RP | 1) Rd10 mice (both sexes, neonatal); 2) BALB/c mice (female, 4-6 weeks old) | 1) Rd10 mutant mice; 2) BALB/c mice (5000 lux for 8 h) | n = 8 per group | Subcutaneous injections (500 mg/kg body weight) | 1) Rd10: once every 3 days, P6 to P30 or P50; 2) BALB/c: one day and again 1 h prior to light exposure, single | 1) Rd10: P30 or P50; 2) BALB/c: Day 1 or Day 7 | The eyeball and whole retina | ERG, Fluorescence labeling, retinal flat-mount, HE staining | Preserve photoreceptor structure and function by anti-oxidative in RP model |
| Arlene V.Drack, 2012 (USA) [60] | RP | 1) Bbs1 mice; 2) Rd10 mice (sex not specified, neonatal) | 1) Bbs1 mutant mice; 2) Rd10 mutant mice | n = 4-6 per group | Subcutaneous injections (500 mg/kg body weight) | 1) Bbs1: twice a week, P40-P120; 2) Rd10: once every 3 days, P6-P38 |
1) Bbs1: P120; 2) Rd10: P30 or P38 | Eye ball | ERG, OCT, HE staining | 1) Preserve of ERG b-waves, the outer nuclear layer(ONL), and prevention of obesity in Bardet-Biedl syndrome mode; 2) Preserved ERG b-waves and the ONL in RP model |
| Agustina Noailles, 2014 (Spain) [61] | RP | P23H rats (sex not specified, neonatal) | P23H mutant rats |
n = 6 or n = 4 per group |
Intraperitoneal injections (500 mg/kg body weight) | Once a week, P20-P120 |
P120 | The eyeball and whole retina | IHC | Reduction of microglial cell number, prevention of activation of microglial cells and inhibition of the number and activation of macrophages, by anti-inflammatory effect in RP model |
| Laura Fernández-Sánchez, 2017 (Spain) [62] | RP | P23H rats (sex not specified, neonatal) | P23H mutant rats | n = 17 per group | Intravitreal injections of TUDCA-loaded PLGA MSs (5.05 ± 0.11 μg TUDCA/mg MSs) | Once a month, P30-P90 or P120 |
P30, P60, P90 and P120 | Eye ball | ERG, immunofluorescence, HE staining | Preserve photoreceptor function and preserve the synaptic contacts of photoreceptors with bipolar and horizontal cells in the RP model |
| Xun Zhang, 2019 (Scotland) [63] | RP | Rpgr knockout mice (both sexes, neonatal) | Rpgr knockout mice | n = 6 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a week, P30-P120 |
P120 | Eye ball | HE staining, immunofluorescence, qRT-PCR, WB, TUNEL staining | Prevention of photoreceptor degeneration and reduction of apoptosis in RP by suppressing microglial activation and inflammation |
| Laura Fernández-Sánchez, 2022 (Spain) [64] | RP | P23H rats (sex not specified, neonatal) | P23H mutant rats | n = 12 or n = 15 or n = 11 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a week, P21-P120 |
P120 | The eyeball and whole retina | Retinal flat-mount, IHC, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry | Neuroprotective effect on photoreceptor cells and protection of vascular and glial degeneration in RP model |
| Eric C. Lawson, 2016 (USA) [65] | RD | Rd1 mice (sex not specified, neonatal) | Rd1 mutant mice | n = 6 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a day, P6-P21 |
P21 | Eye ball | ERG, toluidine blue staining | Preserve function and structure in a model of rapid RD |
| Ye Tao, 2019 (China) [66] | RD | C57BL/6 mice (both sexes, 8 weeks old) | MNU(60 mg/kg body weight single, ip) | n = 40 per group | Subcutaneous injections (500 mg/kg body weight) | Daily for consecutive 7 days for 3 days before and 4 days after MNU | Day 7 after MNU | The eyeball and whole retina | Optokinetic behavioral test, ERG, retinal flat-mount, SD-OC-OCT, HE staining, immunofluorescence, IHC, TUNEL staining, qRT-PCR, Multi-electrode array (MEA) | Protection of visual function(visual acuity, contrast sensitivity, optokinetic performance) and structure by downregulating the levels of apoptosis-related factors Caspase-3, calpain-2, and Bax. Amelioration of the retinal oxidation status by decreasing MDA levels and increasing superoxide dismutase (SOD) contents in the RD model |
| Liping Yang, 2013 (China, USA) [67] | DR | SD rats (female, 8 weeks old, 180g) | STZ(60 mg/kg body weight, single, ip) | n = 18 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a day for 8 weeks, beginning 5 days after STZ | 2, 4, 6, and 8 weeks | The eyeball and whole retina | Retinal flat-mount, immunofluorescence, perfusion labeling, fundus fluorescein angiograph, HE staining, IHC, Real-time PCR, WB | 1) Protection of RGC death in diabetic retinas by inhibiting caspase-12 and p-c-Jun 1 levels; 2) Prevention of neuronal loss and vascular abnormalities by reducing CHOP expression; 3) Prevention of DR by inhibiting the activation of ER stress pathways |
| Chunfei Wang, 2016 (China) [54] | DR | SD rats (male, age not specified, 180-200g) | High glucose fat diet + STZ (30 mg/kg body weight, single, ip) | n = 10 per group | Intraperitoneal injections (750, 500, 250 mg/kg body weight) | Once a day for 2 months | 2 months | Eye ball | ELISA, HE staining, IHC | Amelioration of DR by decreasing NO content and down-regulating the inflammatory factors expression of ICAM-1, NOS, NF-κB p65, and VEGF |
| Jieming Fu, 2021 (USA) [68] | DR | C57BL/6J (both sexes, 8-10 weeks old) | STZ (50 mg/kg body weight, single, IP) |
n = 121 total | Intraperitoneal injections (500 mg/kg body weight) | Twice a week for 10 weeks, starting 1 or 3 weeks after induction of diabetes |
Starting from 4 weeks after STZ, every two weeks or every four weeks | / | Optomotor Response(OMR), ERG | Preserve visual function in type I diabetes model by ameliorating ERG a-wave, b-wave, and OP2 deficits and maintaining spatial frequency and contrast sensitivity threshold |
| Violeta Gómez-Vicente, 2015 (Spain) [69] | RGCs injury | SD rats (sex not specified, 12-16 weeks old) | Intravitreal injection of NMDA (3 μl of 20 mM, single) | n = 5-6 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a day for 6 days | Day 4, day 7 after TUDCA | The eyeball and whole retina | ERG, IHC, retinal flat mount | Protection of retinal function by increasing RGC density |
| Yuta Kitamura, 2019 (Japan) [70] | RGCs injury | SD rats (male, 7-10 weeks old) | Optic nerve crush, single | n = 6 per group | Topical administration (100 mM, one drop) | Once every 12 hours for 14 days | 2 weeks | The eyeball and whole retina | IHC, TUNEL staining | Protection of the densities of RGCs and prevention of axons damage in optic nerve |
| Se Joon Woo, 2010 (Korea) [71] | CNV | BN rats (male, adult) | 512 nm Argon laser photocoagulation, single (spot size of 100 mm, at 150 mW, over 100 ms) | n = 13 per group | Intraperitoneal injections (100 mg/kg body weight) | Once a day, from 1 day before to 14 days after the laser | 14 days after CNV induction | Eye ball | Fluorescein fundus angiography (FFA), HE staining, ELISA | Reduction of CNV fluorescein leakage and lesion size, improvement of vascularity, by suppressing early VEGF elevation in the retina after laser injury, which might be associated with anti-inflammatory action |
| Dimosthenis Mantopoulos, 2011 (USA) [72] | RDT | BN rats (male, adult, 200-250 g) | Transscleral subretinal injection of 50 mml of 1% sodium hyaluronate, single |
n = 6 per group | Intraperitoneal injections (500 mg/kg body weight) | Once a day, first injection 24 hours prior to the induction of RD, the treatment was started 6 hours after RD, for 3day or 5day | 3 and 5 days after RDT induction | Eye ball | TUNEL staining, IHC, ELISA, caspase 2, 3, 8, 9 colorimetric assay, WB | 1) Preserve of photoreceptors after RDT, reduction of apoptosis, which might be associated with suppression of caspases 3 and 9, as well as carbonyl-protein adducts; 2) Reduction of protein oxidation through ROS |
| Tao Zhang, 2012 (USA) [73] | LHON | Lrat-/- mice (sex not specified, neonatal) | Lrat-/- mutant mice | n = 6-8 per group | Subcutaneous injections (500 mg/kg body weight) | Once every 3 days, starting at P9 to P28 | P28 | The eyeball and whole retina | Retinal flat mount, IHC, WB | 1) Reduction of ER stress and apoptosis in Leber’s model; 2) Postponement of cone degeneration and promotion of the degradation of cone membrane-associated proteins by enhancing the ER-associated protein degradation pathway |