Table 1.
Treatments for retinitis pigmentosa and related mechanisms.
| Mechanism | Approach | Gene/molecule/agent | Effect | Model | Ref. |
|---|---|---|---|---|---|
| TNFα signal | Genetic KD TrkC antagonism |
TrkC.T1 KB1368 |
Suppress p-ERK activation and TNFα production | RHOP347S mouse | (71) |
| p75NTR antagonism | THX-B | Inhibit reactive gliosis and TNFα secretion | Rd10, RHOP347S mouse | (72) | |
| Genetic KD | Tnfα | Decrease proinflammatory factors (IL-1β, IL-6, IL-17, RANTES, CCL2) as well anti-inflammatory factor (IL-10 and IL-13) | T17MRHO mouse | (73) | |
| TNFα blockade | Infliximab | Decrease caspase-3 activation and reactive gliosis | Zaprinast-induced degeneration of porcine retina | (74) | |
| Adalimumab | Decrease PARP activation, microglia activation and NLRP3 inflammasome activation | Rd10 mouse | (25, 75) | ||
| TLR signal | Genetic KO | Tlr2 | Suppress microglial activation and infiltration | Rd10, P23H mouse | (76) |
| Genetic KO | Tlr4 | Reduce CCL2 expression, microglia activation and gliosis | LD Abca4-/- Rdh8-/- mouse | (77) | |
| Microglia inhibition | Minocycline | Suppress microglial activation and migration | P23H-1, RCS rat, Prph2 Rd2/Rd2 mouse | (78, 79) | |
| Minocycline | Decrease microglia activation and proinflammatory gene transduction | LD mouse retina | (80, 81) | ||
| Minocycline | Decrease microglia activation and proinflammatory molecule expression | Rd10 mouse | (82) | ||
| Genetic KO | Myd88 | Reduce chemokine (CCL2, CCL4, CCL7 and CXCL10) expression and microglial activation | Rd1 mouse | (83) | |
| MyD88 inhibition | MyD88 inhibitor peptide | Suppress microglia infiltration, increase neuroprotective microglia, expression of MCP-1, IL-27 and crystalline | Rd10 mouse | (84, 85) | |
| AMWAP supplement | AMWAP | Blockade TLR-mediated NF-κB activation | 661W cell-microglia co-culture | (86) | |
| NLRP3 signal | NLRP3 inhibition | N-acetylcysteine | Decrease NLRP3 expression and microglial infiltration | Rd10 mouse, P23H rat | (24, 87) |
| P2X7R blockade | PPADS | Promote photoreceptor survival | Rd1 mouse | (88) | |
| BBG | Decrease inflammasome components (NLRP3, cleaved caspase-1 and mature IL-1β proteins) | P23H rat | (87) | ||
| IL-1β blockade | Anakinra | Reduce photoreceptor apoptosis | Rd10 mouse | (19) | |
| CX3CL1/CX3CR1 | CX3CL1 supplement | CX3CL1 | Decrease microglial infiltration, phagocytosis and activation | Rd10 mouse | (89) |
| AAV8-sCX3CL1 | Improve cone survival | Rd1, rd10 and rhodopsin null mouse | (90) | ||
| Norgestrel | Upregulate CX3CL1/CX3CR1 signal | Rd10 mouse | (91, 92) | ||
| CCL2/CCR2 | CCR2 inhibition | Lecithin-bound iodine Minocycline |
Suppress CCR2 positive macrophage invasion | Mertk mouse | (93, 94) |
| Genetic KO | Ccr2 | Reduce apoptosis | Rd10 | (95) | |
| Ccl2/Ccl3 | Reduce retinal inflammation | Mertk mouse | (96) | ||
| Genetic KD | CCL2 siRNA | Decrease monocyte/microglia infiltration | LD rat retina | (97) | |
| JAK/STAT pathway | JAK/STAT inhibition | AG490 | Improve PR survival | LD mouse retina | (98) |
| OECs transplantation | Inhibit JAK2/STAT3 activity and increase SOCS3 | RCS rat | (99) | ||
| JAK/STAT activation | pMSC-RPCs transplantation | Activate JAK/STAT, improve retinal structure and function | Rd12 | (100) | |
| CNTF supplement | rAAV2/2-hCNTF | Upregulate STAT3, SOCS3, SOCS5 and complement factor (C3, C4a, Cfb) expression | Rhodopsin null mouse | (101) | |
| LV-hCNTF | Stimulate expression of LIF, Edn2; activate gp130/JAK/STAT | Rds/peripherin P216L transgenic mice | (102) | ||
| LIF | Activate STAT3, improves PR survival | LD mouse retina | (103) | ||
| Epigenetic modification | HDACi | Trichostatin A | Decrease activity of PARP, preserve cone survival | Rd1, rd10 mouse | (104, 105) |
| Tubastatin A | Improve cone survival, alter expression about ubiquitin-proteasome, phototransduction, metabolism and phagosome | Zebrafish, atp6v0e1(-/-)zebrafish, rd10 mouse | (106, 107) | ||
| Romidepsin | Inhibit transcription of inflammatory genes and inflammation | Rd10 mouse | (108) | ||
| Valproic acid | Protection varies with genotype | (109, 110) | |||
| BET inhibition | JQ1 | Suppress microglial proliferation, migration, and cytokine production | Rd10 mouse | (111) | |
| LSD1 inhibition | Tranylcypromine; GSK2879552 | Inhibit transcription of inflammatory genes and inflammation | Rd10 mouse | (108) | |
| H3K27me3 inhibition | DZNep | Improve PR survival | Rd1 mouse | (112) | |
| miRNA inhibition | AAV-miRNA modulator of miR-6937 | Improve ONL thickness and ERG response | Rd10 mouse | (113) | |
| miRNA supplement | AAV- miR-204 | Suppress microglia activation | RHO-P347S mouse | (114) | |
| Herbal agent | Curcumin | Inhibit microglia activation and expression of CCL2, TIMP-1, improves retinal morphology | Rd1 mouse, P23H rat | (115, 116) | |
| Lyceum barbarum polysaccharides | Inhibit NF-κB and HIF-1α expression | Rd1, rd10 | (117, 118) | ||
| Zeaxanthin dipalmitate | Inhibit STAT3, CCL2, MAPK pathways | Rd10 mouse | (119) | ||
| Saffron | P2X7R signaling blockade, decrease vascular disruption | ATP-induced PR death, P23H rat | (120, 121) | ||
| Resveratrol | Downregulate microglial migratory, phagocytic, and proinflammatory cytokine production | Microglia-mediated 661W death | (122) | ||
| JC19 | Improve PR survival, sirtuin1 activation may be the protective mechanism | Rd10 mouse | (123) |
THX-B, (1,3-diisopropyl-1-[2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro_purin-7-yl)-acetyl]-urea; KD, knock down; KO, knock out; LD, light damage; MyD88, myeloid differentiation factor 88; AMWAP, activated microglia/macrophage whey acidic protein; PPADS, pyridoxal-phosphate-6-azophenyl-2’,4’-disulfonic acid; BBG, Brilliant Blue G; AAV, adeno-associated virus; siRNA, small interfering RNA; PR, photoreceptor; OECs, olfactory ensheathing cells; SOCS, suppressor of cytokine signaling; pMSC-RPCs, primitive mesenchymal stem cell-derived retinal progenitor cells; rAAV2/2, recombinant adeno-associated virus serotype 2; LV, lentiviral vector; LIF, leukemia inhibitory factor; Edn2, endothelin2; HDACi, histone deacetylase inhibition; BET, bromodomain and extraterminal domain; LSD1, lysine demethylase 1; miRNA, microRNA; ONL, outer nuclear layer; ERG, electroretinogram; TIMP-1, tissue inhibitor of metalloproteinases 1.