Hidehiro Oku

Ocular blood flow changes after dynamic exercise in humans

PurposeTo investigate control mechanisms for ocular blood flow changes after dynamic exercise using two different methods.MethodsChanges over time in the tissue blood flow in the retina and choroid-retina of healthy volunteers were determined after dynamic exercise (Masters double two-step test), using scanning laser Doppler flowmetry (SLDF) and laser speckle flowgraphy (LSFG). Changes in intraocular pressure (IOP), blood pressure, plasma CO2 gas concentration (pCO2), and levels of nitric oxide (NO) metabolites were examined.ResultsRetinal blood flow measured by SLDF increased significantly only at 15 min after exercise. In contrast, normalized blur (NB) values in the choroid-retina, obtained by LSFG, increased significantly up to 60 min after exercise. Ocular perfusion pressure (OPP), calculated from IOP and blood pressure, increased significantly immediately and 15 min after exercise. The plasma NO metabolite levels increased significantly, although pCO2 levels were unchanged.ConclusionsDynamic exercise changes OPP and produces increased tissue blood flow in the retina in the immediate postexercise period, while blood flow increases more persistently in the choroid-retina. Difference in control of blood flow in these two regions may be related to stronger autoregulatory mechanism of blood flow in the retina. Nitric oxide may play a role in the regulation of blood flow.

Reduced retinal function in amyloid precursor protein-over-expressing transgenic mice via attenuating glutamate-N-methyl-d-aspartate receptor signaling.

Here, we examined whether amyloid‐β (Aβ) protein participates in cell death and retinal function using three types of transgenic (Tg) mice in vivo [human mutant amyloid precursor protein (APP) Tg (Tg 2576) mice, mutant presenilin‐1 (PS‐1) knock‐in mice, and APP/PS‐1 double Tg mice]. ELISA revealed that the insoluble form of Aβ1‐40 was markedly accumulated in the retinas of APP and APP/PS‐1, but not PS‐1 Tg, mice (vs. wild‐type mice). In APP Tg and APP/PS‐1 Tg mice, immunostaining revealed accumulations of intracellular Aβ1–42 in retinal ganglion cells and in the inner and outer nuclear layers. APP Tg and APP/PS‐1 Tg, but not PS‐1 Tg, mice had less NMDA‐induced retinal damage than wild‐type mice, and the reduced damage in APP/PS‐1 Tg mice was diminished by the pre‐treatment of N‐[N‐(3,5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester, a γ‐secretase inhibitor. Furthermore, the number of TUNEL‐positive cells was significantly less in ganglion cell layer of APP/PS‐1 Tg mice than PS‐1 Tg mice 24 h after NMDA injection. The phosphorylated form of calcium/calmodulin‐dependent protein kinase IIα (CaMKIIα), but not total CaMKIIα or total NMDA receptor 1 (NR1) subunit, in total retinal extracts was decreased in non‐treated retinas of APP/PS‐1 Tg mice (vs. wild‐type mice). CaMKIIα and NR2B proteins, but not NR1, in retinal membrane fraction were significantly decreased in APP/PS‐1 Tg mice as compared with wild‐type mice. The NMDA‐induced increase in p‐CaMKIIα in the retina was also lower in APP/PS‐1 Tg mice than in wild‐type mice. In electroretinogram and visual‐evoked potential recordings, the implicit time to each peak from a light stimulus was prolonged in APP/PS‐1 mice versus wild‐type mice. Hence, Aβ may impair retinal function by reducing activation of NMDA‐receptor signaling pathways.

Electroretinographic study of spontaneously diabetic Torii rats

Spontaneously diabetic Torii (SDT) rats are an inbred strain of rats with a non-obese type 2 diabetes mellitus that were isolated from an outbred colony of Sprague–Dawley (SD) rats. Electroretinograms (ERGs) were recorded from SDT and SD (controls) rats at 10- and 44-weeks-of-age to determine their retinal function. The amplitudes and implicit times of the ERGs of the right and left eyes were not significantly different indicating that the intra-individual variation was small. Both amplitudes and implicit times of the ERGs in the SDT rats were not significantly different from those of SD rats at 10-weeks-of-age. At 44-weeks-of-age, however, the a- and b-waves and the oscillatory potentials were significantly reduced with prolonged implicit times in the SDT rats compared to SD rats. These depressed ERGs may reflect vascular and neuronal damage throughout the retina as are seen in the advanced stages of human diabetic retinopathy. Thus, the SDT rat can be used to study the retinal physiology of diabetic retinopathy.

Peripheral cone dystrophy in an elderly man.

tumors of the ocular fundus. Classification and clinical manifestations in 103 patients. Arch Ophthalmol 1995; 113: 615–23. 3. Osman SA, Aylin Y, Arikan G, Celikel H. Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I. Clin Experiment Ophthalmol 2007; 35: 191–3. 4. Khan JA, Ide CH, Strickland MP. Coats’-type retinitis pigmentosa. Surv Ophthalmol 1988; 32: 317–32. 5. Shields JA, Shields CL, Honavar SG, Demirci H. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture. Am J Ophthalmol 2001; 131: 561–71.

Endothelin-1 (ET-1) is increased in rat retina after crushing optic nerve.

Purpose: To determine the alterations in the expression of endothelin-1 (ET-1) and its specific receptors in the sensory retina after optic nerve injury. Methods: The optic nerve of the right eye of Wistar rats was crushed. The sensory retinas were removed 1, 2, 4, 7, and 14 days after the surgery, and the amount of ET-1 in the retinas was measured by radioimmunoassay, and the mRNA levels of ETA and ETB receptors were determined by real-time PCR. Results: The ET-1 levels in the sensory retinas following the optic nerve crush were 8.83 ± 2.23 and 9.99 ± 4.83 pg/mg protein on days 7 and 14 after the injury, while those in the sham controls were 4.55 ± 1.36 and 4.85 ± 1.57 pg/mg protein, respectively. The increase was significant on day 7 (p = 0.003, ANOVA followed by t− test), but not on day 14 (p = 0.054). The mRNA levels of the ETA and ETB receptors in the retina after the optic nerve crush was significantly increased on day 7. A two-fold increase was recognized in ETB receptors. Immunohistochemical analyses revealed that the ET-1 expression was increased mainly in the inner retinal layers, including the nerve fiber layer and ganglion cell layer (GCL). The increased immunoreactivity of the ETB receptor was seen in the GCL cells and also in the outer nuclear layer. Conclusion: An increase in the intraretinal ET-1 may be involved in the retinal remodeling after the optic nerve is crushed.

Abnormalities of visual-evoked potentials and pupillary light reflexes in a family with autosomal dominant occult macular dystrophy

Occult macular dystrophy (OMD) is an unusual inherited or sporadic macular dystrophy characterized by an essentially normal appearing ocular fundus and normal ocular circulation determined by fluorescein angiography but with a progressive decrease of visual acuity. We present a family with OMD who have a delay in the implicit times of both the visual‐evoked potentials and the pupillary light reflexes. Because these delays are usually indicative of optic nerve disorders, deciding on a diagnosis between OMD and optic nerve disorder should be done carefully. We are not aware of any studies that have reported these findings in patients with OMD.

Shift of temporal responsivity curve of pattern reversal visually evoked potentials to lower frequencies in patients after recovery from optic neuritis

Purpose:  To investigate the responsivity of the visual system to pattern reversal stimuli of different reversal rates in optic neuritis patients after a full recovery of visual acuity.