Proliferative vitreoretinopathy (PVR) is a main cause of failure in retinal reattachment surgery. There have been many studies about the inhibition of proliferative vitreoretinophthy with several drugs. Authors investigated the inhibitory effect of proliferative vitreoretinopathy and retinal toxicity with various concentration of daunorubicin after intravitreal injection into the eyes of the pigmented rabbit. 7 pigment rabbit (11eyes) were used as subjects. After lensectomy and vitrectomy, control group was injected dermal fibroblast and F-BSS, and treatment group was injected dermal fibroblast and 5, 10, 15, 30 nmol Daunorubicin. At two weeks after intravitreal injection, both group were enucleated and examined with gross finding, light--microscopy, and electronmicroscopy. In all control group, proliferative vitreoretinopathy was found, but only preretinal membrane formation was found in 5, 10 nmol Daunorubicin injected group. In 15 nmol Daunorubicin injected group, the retina structure was preserved normally. In 30 nmol Daunorubicin injected group, the retinal outer segment was degenerated in microscopic finding. These results show that Daunorubicin has a potent effect on proliferative vitreoretinopathy, especially in 15 nmol, but retinal toxicity is suspected in marethan 30 nmol.
Daunorubicin* ; Fibroblasts ; Intravitreal Injections ; Membranes ; Retina ; Retinal Photoreceptor Cell Outer Segment ; Retinaldehyde ; Vitrectomy ; Vitreoretinopathy, Proliferative*

PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) compared with observation for treating acute central serous chorioretinopathy (CSC). METHODS: A retrospective study of 36 patients with acute CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15 patients with observation (observation group). Patients in the anti-VEGF group received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of the foveal inner segment/outer segment (IS/OS) line at 12 months was also analyzed. RESULTS: Resolution of SRF was achieved in 20 of 21 eyes in the anti-VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA and CFT were not different between the two groups at 12 months (p > 0.05). The amount of change in BCVA, however, differed significantly between the groups (p = 0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF group than in the observation group (p = 0.012). CONCLUSIONS: In terms of BCVA, anti-VEGF and observation only had similar therapeutic effects in acute CSC patients. In some patients, however, the rapid resolution of SRF by anti-VEGF might reduce the risk of photoreceptor degeneration and improve long-term visual acuity.
Acute Disease ; Adult ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/therapeutic use ; Central Serous Chorioretinopathy/*drug therapy/physiopathology ; Female ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Observation ; Ranibizumab/therapeutic use ; Retinal Photoreceptor Cell Inner Segment/pathology ; Retinal Photoreceptor Cell Outer Segment/pathology ; Retrospective Studies ; Subretinal Fluid/drug effects ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

PURPOSE: To investigate which spectral domain optical coherence tomography (SD-OCT) findings predict visual outcome after anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (NV-AMD). METHODS: We reviewed the medical records of patients with treatment-naive NV-AMD who underwent three or more consecutive anti-VEGF injections. The patients were divided into three groups according to their changes of visual acuity (VA); improved (group I), static (group S), or worsened (group W). We assessed the incidences and values of all available SD-OCT findings of these groups, compared these findings between the three groups and compared the initial values with the post-treatment values. RESULTS: Better initial VA and longer external limiting membrane (ELM) length were associated with less change in VA after anti-VEGF treatment. The initial VA was mildly correlated with initial photoreceptor inner and outer segment junction (IS/OS) length and initial ELM length. The final VA was also mildly correlated with the final IS/OS length and the final ELM length. VA was significantly changed after anti-VEGF treatment in groups W and I. With regard to incidence, disruption of the IS/OS (IS/OS-D), disruption of the ELM (ELM-D) and ELM length differed significantly between the three groups, particularly ELM-D. The incidences of IS/OS-D and ELM-D in group I were significantly lower than those in groups S and W, and those in group S were also lower than those in group W. The ELM length in group I was significantly longer than it was in groups S and W, and the ELM length in group S was longer than that for group W. However, these three findings did not change after the anti-VEGF treatment. CONCLUSIONS: Initial IS/OS-D, ELM length and particularly ELM-D can be useful predictors of the visual outcome after anti-VEGF treatment in NV-AMD patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*therapeutic use ; Choroidal Neovascularization/*drug therapy/physiopathology ; Female ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Ranibizumab/*therapeutic use ; Retinal Photoreceptor Cell Inner Segment/pathology ; Retinal Photoreceptor Cell Outer Segment/pathology ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/*physiology ; Wet Macular Degeneration/*drug therapy/physiopathology

After the immunization of pigmented guinea pigs with bovine rod outer segments in complete Freund's adjuvant, the regional lymph nodes were excised, teased and sedimented by centrifugation. These fresh lymphocytes were injected intravitreally (a single injection of 10 X 10 cells in 50 micro l) in 18 eyes. The involvement of the ciliary body and the choroid with polymorphonuclear leucoytes and later with round cells was noted in 16 eyes. Destructions of the visual cells of the retina were demonstrated in 8 eyes. When the fresh lymphocytes were injected subconjunctivally (50 X 10 cells in 30 micro l) four times. four of the 8 eyes showed slight infiltrations of the ciliary body and the choroid with round cells. No retinal lesion was found. Following repeated freezing and thawing of the lymphocytes. transfer experiments wereperformed with the nonviable cells and their extracts respectively. In 8 eyes injected intravitreally with nonviable cells. 2 eyes showed the infiltration of the uvea with round cells, whereas. of 6 eyes injected subconjunctivally, only one eye showed such changes. The extracts of lymphocytes were injected intravitreally in 8 eyes of which 5 eyes demon-strated moderate degree of infiltration of the uvea. Of 2 eyes injected subconjunctivally, 2 eyes. showed slight histological changes. As control experiments, lymphocytes taken from animals immunized. only with the adjuvant were treated as before and transferred to normal animals. Only one eye of 3 eyes received single intravitreal injection of fresh cells showed slight degree of infiltration of the uvea. Thus it can be concluded that the experimental autoimmune uveitis in guinea pigs could be transferred to normal animals by the transfer of non-viable lymphocytes and especially by their extracts.
Animals ; Centrifugation ; Choroid ; Ciliary Body ; Freezing ; Freund's Adjuvant ; Guinea Pigs ; Immunization ; Intravitreal Injections ; Lymph Nodes ; Lymphocytes ; Retina ; Retinaldehyde ; Rod Cell Outer Segment ; Uvea ; Uveitis*

Passive transfer experiments were performed by local administrations of sera from guinea pigs hyperimmunized by bovine rod outer segments with complete Freund's adjuvant in random-bred guinea pigs. Routes of administrations were(1) single intravitreal injection of serum (25 micrl l, in 18 eyes), (2) the intravitreal injection associated with 2 subconjunctival injections (150 micrl l, in 9 eyes), (3) three subconjunctival injections of serum (150 micrl l, in 6 eyes), (4) five subconjunctival injections of serum with 2 paracenteses (in 14 eyes) and (5) four injections into the anterior chamber (50 micrl l) with 2 subconjunctival injections (in 4 eyes). Clinically animals showed cells in the anterior vitreous in 50-83% of cases. Histologically infltrations of round cells, focal or diffuse, were noted in the choroid with scattered polymorphonuclear, eosino and plasma cells. In the retina disappearance of visual cells was found, sometimes complicated by the involvement of the bipolar cells in severe cases. These findings were quite similar to the lesions produced in actively immunized animals. Choroidal lesions were most frequently found. Serum taken from the enucleated donors, and concentrated serum were more effective in the production of this transfer disese. The control experiments in which normal serum or serum immunized by adjuvant alone, revealed very low incidence of ocular lesions which were generally mild in degree. It can be concluded that humoral immunity also plays very important roles in the pathogenesis of autoimmune uveoretinitis.
Animals ; Anterior Chamber ; Choroid ; Freund's Adjuvant ; Guinea Pigs ; Humans ; Immunity, Humoral ; Incidence ; Intravitreal Injections ; Paracentesis ; Plasma Cells ; Retina ; Rod Cell Outer Segment ; Tissue Donors

This study was designed to determine the maximal safe drug concentration of intravitreal ciprofloxacin in phakic rabbit eyes. Twenty-two eyes of New Zealand pigmented rabbits received midvitreal ciprofloxacin of 100, 200, 400, 600 or 800 microgram in BSS Plus, or BSS Plus only. Retinal toxicity was dose-dependent as determined with electroretinography, light microscopy, and transmission electron microscopy. At a dose of greater than 400 microgram, disorganization of the outer segments was a main pathological finding in transmission electron microscopy. We evaluated retinal function by measuring the electroretinograms for a graded series of flash intensities and by fitting electroretinogram b-wave amplitudes to the Naka-Rushton equation. At a dose of greater than 600 microgram, Rmax was significantly decreased and log K was significantly increased. N-value tended to decrease. A decrease of b-wave amplitudes caused by retinal toxicity could be detected very sensitively with lower luminance stimuli. Determination of retinal toxicity with lower luminance electroretinography revealed a significant decrease of b-wave amplitudes at a dose of greater than 400 microgram. We concluded that a safe dose of intravitreal ciprofloxacin in phakic rabbit eyes was 200 microgram in phakic eyes.
Animals ; Ciprofloxacin/administration & dosage/*toxicity ; Dose-Response Relationship, Drug ; Electroretinography/drug effects ; Injections ; Lens, Crystalline ; Photic Stimulation ; Rabbits ; Retina/*drug effects/pathology/physiopathology ; Rod Cell Outer Segment/drug effects/pathology ; Vitreous Body

Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound forms. Ras is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through more than one signaling pathway. The Ras-effector proteins contain a Ras-associating (RA) domain through which these associate with Ras in a GTP-dependent manner. The RA domain is highly conserved among the members of the growth factor receptor-bound (Grb) 7 family of proteins which includes Grb7, Grb10 and Grb14. Our laboratory has reported an unusual observation that RA domain of Grb14 binds to the C-terminal nucleotide binding site of cyclic nucleotide gated channel (CTRCNGA1) and inhibits the channel activity. Molecular modeling of the CTR-CNGA1 displays 50%-70% tertiary structural similarity towards Ras proteins. We named this region as Ras-like domain (RLD). The interaction between RA-Grb14 and RLD-CNGA1 is mediated through a simple protein-protein interaction temporally and spatially regulated by light and cGMP. It is interesting to note that Grb14 binds to GTPase-mutant Rab5, a Ras-related small GTPase whereas Grb10 binds only to GTP-bound form of active Rab5 but not to GTPase-defective mutant Rab5. These results suggest that Grb14 might have been evolved later in the evolution that binds to both Ras and nucleotide binding proteins such as CNGA1. Our studies also suggest that eukaryotic CNG channels could be evolved through a gene fusion between prokaryotic ion channels and cyclic nucleotide binding proteins, both of which might have undergone several sequence variations for functional adaptation during evolution.
Amino Acid Sequence ; Animals ; Cattle ; Cell Membrane ; metabolism ; radiation effects ; Conserved Sequence ; Cyclic Nucleotide-Gated Cation Channels ; genetics ; metabolism ; Evolution, Molecular ; Female ; GRB7 Adaptor Protein ; chemistry ; genetics ; metabolism ; HEK293 Cells ; Humans ; Light ; Male ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; radiation effects ; Protein Structure, Tertiary ; Protein Transport ; Rats ; Rod Cell Outer Segment ; radiation effects ; rab5 GTP-Binding Proteins ; metabolism ; ras Proteins ; metabolism