Table 1.
Studies using DARC imaging.
| Focus of Study | Model | Finding | Reference |
|---|---|---|---|
| Proof of concept | Rat | First retinal cell apoptosis imaging with DARC in vivo. Histological validation of the DARC technique confirms apoptosing RGCs. | [104] |
| IOP (Pathogenesis) | Rat | RGC apoptosis is strongly correlated with elevated IOP, and changes to the extra-cellular matrix induced by raised IOP. | [107] |
| NMDA receptor antagonism (Treatment) | Rat | Demonstration of a staurosporine-induced rat ocular hypertension model in testing neuroprotective strategies. Broad-spectrum NMDA receptor antagonist MK801 is a more effective neuroprotector than NR2B-selective NMDA receptor antagonist ifenprodil, especially when combined with group II mGluR agonist LY354740. | [108] |
| Beta-amyloid (Pathogenesis) | Rat | Beta-amyloid, implicated in Alzheimer’s disease, co-localizes with apoptosing retinal ganglion cells, and induces RGC apoptosis in a time and dose-dependent manner. | [109] |
| Diabetic retinopathy (Pathogenesis) | Mouse | RGC apoptosis was significantly higher in transgenic diabetic mice at eight weeks of age when compared to normal controls, suggesting DARC may be useful in early detection of diabetic retinopathy. | [106] |
| Laser exposure (Pathogenesis) | Rat | First use of DARC to image inner nuclear layer apoptosis after laser treatment with frequency-doubled Nd:YAG retinal laser. Increasing duration and power of laser led to more inner retinal layer involvement, with dose-dependent correlation of laser exposure and DARC spot density, along with lesion area and elevation. | [110] |
| Light damage (Pathogenesis) | Rat | In vivo demonstration of outer nuclear layer apoptosis in response to blue light exposure. Histological analysis confirmed photoreceptor death. | [111] |
| Proof of concept | Rat | Spectrally distinct fluorescent markers were used to monitor both early and late apoptosis and necrosis in individual cells, in real-time. | [112] |
| Dry AMD (Pathogenesis) | Mouse | Identification of photoreceptor apoptosis in dry age-related macular degeneration (AMD). | [113] |
| Amyloid-beta (Treatment) | Rat | A dose-dependent neuroprotective effect from systemic injections of the amyloid-beta aggregation modulator MRZ-99030. | [114] |
| DONS (Treatment) | Rat | A novel method of direct optic nerve sheath (DONS) delivery of Schwann cells in a partial optic nerve transection model of secondary degeneration is protective against RGC apoptosis, compared to intravitreal delivery. | [115] |
| Adenosine A3 agonists (Treatment) | Rat | 2-Cl-IB-MECA, a selective adenosine A3 agonist, is neuroprotective in vitro and in vivo. | [116] |
| Rosiglitazone (Treatment) | Rat | DARC used to demonstrate retinal changes in a rodent model of Parkinson’s disease. An enhanced neuroprotective effect against rotenone-induced damage was seen with liposome-encapsulated rosiglitazone. | [117] |
| Brimonidine (Treatment) | Rat | IOP-independent neuroprotective effect of alpha2 adrenergic receptor agonists (α2ARAs) brimonidine and clonidine. | [118] |
| Coenzyme Q10 (Treatment) | Rat | Topical coenzyme Q10 has a significant neuroprotective effect in a surgically-induced ocular hypertension model of glaucoma. | [119] |
| Proof of concept | Human | Intravenous ANX776 is a safe way to monitor rates of RGC apoptosis in humans using DARC imaging. A significant difference in DARC count was seen between progressing glaucoma patients and healthy controls. | [91] |
| Memantine (Treatment) | Rat | Memantine is an NMDA receptor antagonist, used in the treatment of Alzheimer’s disease. Topical memantine-loaded PLGA-PEG nanoparticles significantly reduced RGC loss in an experimental glaucoma model. | [120] |