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| November 2004 | Inside IOVS | Volume 45/11 |
Cytokine-Induced Corneal Allograft Failure
Corneal transplantation is the most commonly performed graft procedure worldwide; however, immunological rejection accounts for the majority of corneal allograft failures. Damage and subsequent loss of the corneal endothelial cells (CEC), which are essential constituent cells for corneal function, are often a result of rejection. Currently, the exact effector molecules of CEC damage during corneal allograft rejection are unknown. Sagoo et al. (p. 3964) describe a novel mechanism of CEC damage caused by the synergistic activity of pro-inflammatory cytokines TNF, IL-1 and IFNg generating cytotoxic levels of NO. Cytokine-induced apoptosis of corneal endothelium presents a new target for development of anti-rejection therapies.
LASIK Adversely Affects Contrast Sensitivity
The exact influence of laser in situ keratomileusis (LASIK) on visual function and ocular optics has been controversial. In a prospective study, Yamane et al. (p. 3986) evaluated the relation between induced changes in higher-order aberrations of the eye and changes in contrast sensitivity by conventional LASIK for myopia. In 200 eyes of 110 consecutive patients, the surgery significantly improved logMAR best corrected visual acuity, but significantly reduced contrast sensitivity and low-contrast visual acuity. Higher-order wavefront aberrations significantly increased by LASIK. The induced changes in ocular higher-order aberrations showed significant correlations with changes in contrast sensitivity and low contrast visual acuity. It was indicated that the conventional LASIK significantly increases ocular higher-order aberrations, which compromise postoperative contrast sensitivity function.
Absent Corneal Nerves after LASIK
Calvillo et al. (p. 3991) examined nerves in 17 corneas by confocal microscopy preoperatively and for 3 years after LASIK. They found a near absence of subbasal nerves 1 to 3 months postoperatively, which recovered to barely 50% of the preoperative density by 2 years. Median nerve density did not increase between 2 and 3 years. Further studies are needed to measure the effect of this morphologic change on nerve function. The long-term consequences of these changes on corneal clarity and vision are unknown.
Ultrahigh Resolution Full-Field Optical Coherence Tomography (OCT)
A new technique called ultrahigh resolution full-field optical coherence tomography (OCT), which uses a white light source, allows bidimensional non-invasive tomographic imaging without scanning. Grieve et al. (p. 4126) applied full-field OCT to ocular tissue imaging. Unstained tissue samples (cornea, lens, retina, choroid and sclera) and whole unfixed eyes of rat, mouse and pig were examined under immersion. Cellular-level imaging was achieved with high penetration depth. Although the current system is unsuitable for clinical use, this simple technique has potential for in vivo ocular examination.
A High-Resolution Retinal Prosthesis Interface
Retinal prosthetic devices that utilize microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Leng et al. (p. 4132) use microcontact printing to direct retinal ganglion cell neurites to precise and close stimulation positions, allowing for the possibility of a higher density of stimulation sites on retinal prosthetic chips. Ultimately, this may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.
Hepatocyte Growth Factor Protects Photoreceptors from Degeneration
Hepatocyte growth factor (HGF) was first purified from the plasma of patients with fluminant hepatic failure. Thereafter, it has been shown that HGF has various biological effects including regulation of cell survival. Machida et al. (p. 4174) demonstrated that a single injection of HGF led to the morphological and physiological preservation of photoreceptors, when it was intravitreally injected into eyes of commonly used animal models, light-damaged and RCS rats. TUNEL study indicated that an anti-apoptotic effect may be the mechanism for the neuroprotective action of HGF. These findings open a possibility that HGF could be used as a therapeutic agent against photoreceptor degeneration.
BDNF Improves Retinal Structure and Function after PDT
Verteporfin photodynamic therapy (PDT), using laser activation of a photosensitizing dye to close choroidal neovascularization (CNV), is the treatment of choice for subfoveal CNV in patients with age-related macular degeneration. While PDT preferentially affects CNV, it can also damage the overlying retina resulting in reduced vision. Paskowitz et al. (p. 4190) injected brain-derived neurotrophic factor (BDNF) intravitreally 2 days prior to PDT in normal rats. The study demonstrates reduced retinal damage, measured by quantitative histology, and improved vision, measured using multifocal ERG, after PDT in eyes treated with BDNF compared to contralateral control eyes. Their findings demonstrate it may be possible to ameliorate or prevent collateral damage and loss of vision from PDT using adjunctive neuroprotective therapy.
Heme Oxygenase-1 Protects Müller Cells from Retinal Ischemia-Reperfusion Injury
Heme oxygenase-1 (HO-1) is one of the heat shock proteins and plays a role as anti-oxidant, anti-apoptotic, and anti-inflammatory agents. Arai-Gaun et al. (p. 4226) showed that HO-1 was induced in Müller cells after an ischemia-reperfusion injury. Inhibition of HO-1 by siRNA induced Müller cell death and invasion of inflammatory cells, and severer destruction of the retinal architecture occurred after the injury. This study shows that HO-1 promotes the survival of Müller cells against the ischemia-reperfusion injury and also protects the whole retina in the injury.
TGF-b Protects Patients against Proliferative Vitreoretinopathy
Transforming growth factor-b2 (TGF-b2) has been proposed as a local stimulator of proliferative vitreoretinopathy (PVR). The hypothesis is based on elevated levels found in vitreous of PVR patients. Dieudonné et al. (p. 4113), however, found decreased TGF-b2 levels in subretinal fluids that were predictive for later PVR development. These fluids were aspirated at an earlier time point than vitreous, i.e., at the time of primary surgery when PVR was still absent, explaining the different findings. The authors conclude that high TGF-b2 levels at the time of primary surgery may protect patients against subsequent PVR. Their findings suggest that recent views on therapeutic TGF-b2 strategies for preventing PVR need important adjustments.
Adjacent Regions of High Retinal Autofluorescence and Visual Acuity in Retinitis Pigmentosa
Robson et al. (p. 4119) examined patients with retinitis pigmentosa and normal visual acuity that manifest an abnormal parafoveal ring of high density fundus autofluorescence. Suprathreshold and threshold measures of macular function suggest that the high density rings encircle central areas of preserved photopic sensitivity and correspond with the internal edge of visual field constriction. Scotopic sensitivity losses encroach upon areas within the ring of high density and may reflect dysfunction before accumulation of lipofuscin. The presence of normal or slightly increased autofluorescence in surrounding areas suggests the presence of intact photoreceptors that may in future be amenable to functional rescue.
Methimazole-Induced Neovascularization
The anti-thyroid drug methimazole reduces serum L-thyroxine (T4) and serum insulin-like growth factor 1 (IGF-1). A reduction of serum IGF-1, followed by recovery, has been previously implicated in neovascularization of immature retinae, e.g., in retinopathy of prematurity (ROP). Mookadam et al. (p. 4145) found that treating neonatal rats with methimazole resulted in retarded normal retinal vascularization and development of preretinal neovascularization similar to ROP and was associated with initially lower serum T4 and IGF-1. Neovascularization was no worse in conditions of greater serum IGF-1 recovery. These results are consistent with a role for early reduced serum IGF-1 in the pathogenesis of preretinal neovascularization but are contrary to a purely permissive role.
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