Acute Aminoglycoside Retinal Toxicity In Vivo and In Vitro

Hancock, Heather; Guidry, Clyde; Read, Russell W.; Ready, Edgar L; Kraft, Timothy W.

doi:10.1167/iovs.05-0604

Cited by 52 publications

(31 citation statements)

References 23 publications

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“…Retinas were analyzed 40 min after 4-CIN treatment, given that the largest functional changes in the electroretinogram are observed at this time (13). Anatomic analysis showed that the saline and 4-CIN injections resulted in areas of retinal detachment and hemorrhages similar to those reported by Hancock et al (46). Intravitreal injections cause a break in the blood-retina barrier, and the increase in metabolite levels in SD and P23H-3 saline-injected retinas (see Fig.…”

Section: Methodssupporting

confidence: 54%

Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa

Acosta¹,

Shin²,

Ready³

et al. 2010

American Journal of Physiology-Cell Physiology

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-We determined the metabolic changes that precede cell death in the dystrophic proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal SpragueDawley (SD) rat retina. Metabolite levels and metabolic enzymes were analyzed early in development and during the early stages of degeneration in the P23H-3 retina. Control and degenerating retinas showed an age-dependent change in metabolite levels and enzymatic activity, particularly around the time when phototransduction was activated. However, lactate dehydrogenase (LDH) activity was significantly higher in P23H-3 than SD retina before the onset of photoreceptor death. The creatine/phosphocreatine system did not contribute to the increase in ATP, because phosphocreatine levels, creatine kinase, and expression of the creatine transporter remained constant. However, Na ϩ -K ϩ -ATPase and Mg 2ϩ -Ca 2ϩ -ATPase activities were increased in the developing P23H-3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an environment of increased LDH, ATPase activity, and higher-than-normal ATP levels. We tested the effect of metabolic challenge to the retina by inhibiting monocarboxylate transport with ␣-cyano-4-hydroxycinnamic acid or systemically administering the phosphodiesterase inhibitor sildenafil. Secondary to monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate alterations in metabolic activity. However, administration of sildenafil significantly reduced LDH activity in the P23H-3 retina and increased the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an increase in apoptotic markers secondary to inhibition of a phototransduction enzyme (phosphodiesterase), suggesting increased susceptibility to altered cation entry.phosphocreatine; ATP; ␣-cyano-4-hydroxycinnamic acid; sildenafil; lactate dehydrogenase; ATPase RETINITIS PIGMENTOSA is the term given to a family of retinal disorders that cause blindness due to gradual loss of photoreceptors. Although photoreceptor cell death in retinitis pigmentosa has a number of underlying causes that include rhodopsin mutations (94), altered photoreceptor oxygen environment (36,103,104), disk morphogenesis, retinal pigment epithelium dysfunction, and chronic activation of photoreceptor transduction cascade (80), the understanding of the cell death pathways is still evolving. It is generally accepted that cell death in inherited forms of retinal degeneration occurs via the process of apoptosis (16,66,82,92), an active cellular process requiring energy (25). The concept of apoptosis as the major pathway of cell death in inherited forms of retinal degeneration has recently been questioned with a proposal that nonapoptotic pathways also contribute to photoreceptor death (7,23,42,63,86,107).Increased metabolic activity is a potential cause of photoreceptor death in some models of retinal dystrophy, such as the rd/rd (rd1) model, where cyclic nucleotide channels are malfu...

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Section: Methodssupporting

confidence: 54%

Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa

Acosta¹,

Shin²,

Ready³

et al. 2010

American Journal of Physiology-Cell Physiology

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“…4), which is similar to that seen late after central retinal artery occlusion. However, other studies suggest that aminoglycoside toxicity is not fully explained by a vascular mechanism and there may be a mixed-mechanism etiology for this toxicity as well [13]. …”

Section: Discussionmentioning

confidence: 99%

Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

et al. 2016

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Aims: To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods: This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results: Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions: Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

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“…Nevertheless, an intravenous treatment with enrofloxacin prior to vitrectomy did not alter the cultivation of leptospires from vitreal samples significantly (Popp et al 2013). Besides the influence of gentamicin on cultivation attempts, its retinal toxicity needs to be considered (D'amico et al 1984, Hancock et al 2005, Mochizuki et al 1988. Not only the gentamicin-concentration, but also the ocular pigmentation and the manner of application can influence the toxic effects of gentamicin on the retina (Peyman et al 1974, Zemel et al 1995.…”

Section: Discussionmentioning

confidence: 99%

“…Even very low amounts of undiluted gentamicin (30 µg) injected into the vitreous body with the tip of the needle pointing to the retina can cause damage to the retina, whereas an amount of 200 µg of gentamicin did not cause any damage, if the needle was pointed to the anterior segment (Peyman et al 1974). Gentamicin is a strong acid and its toxic effects on the retina may be due to a direct pH-effect on the retinal vasculature and neurons (Hancock et al 2005, Snider et al 1985. The gentamicin-concentration of flushing solution used for vitrectomy of horses varies in the literature between 80 µg/ml and 200 µg/ml as far as noted, and no toxic side effects of the gentamicin in the flushing solution were described so far.…”

Section: Discussionmentioning

confidence: 99%

Detection of intraocular leptospiral DNA, antibodies and Leptospira spp. in horses with equine recurrent uveitis in different laboratories

Baake¹,

Borstel²,

Rohn³

et al. 2016

PHK

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Summary: Equine recurrent uveitis (ERU) is an ocular disease characterized mainly by recurrent episodes of inflammation, alternating with quiescent episodes of various durations. There are numerous aetiological theories for the cause of ERU, but to date, the "classic ERU" is most commonly associated with an intraocular leptospiral infection. The pars plana vitrectomy has, so far, been the most promising treatment of ERU and is thought to be more successful in eyes with detectable leptospiral antibodies in the microscopic agglutination test (MAT) and therefore a preselection is recommended. The objective of this study was to investigate whether different laboratories have an influence on the frequency of detection of leptospiral DNA and leptospiral antibodies from vitreal samples of horses with ERU and if these results are in accordance with cultural testing of the vitreal samples. Vitreal samples were obtained from 93 eyes of 78 horses of various breeds and age with a clinical history of ERU. The vitreal samples were taken at the beginning of the vitrectomy to keep the dilution of the vitreal samples as low as possible. The samples were split and sent to three different laboratories in Germany (L1, L2 and L3). Laboratory 1 (L1) performed a polymerase chain reaction (PCR) and a MAT, laboratory 2 (L2) carried out a PCR and laboratory 3 (L3) performed a MAT, a cultural examination and an enzyme-linked immunosorbent assay on the vitreal specimens. The amount of dilution was evaluated by comparing the urea content of 34 vitreal samples with the urea content of the serum of each of the horses at the time of sampling. Furthermore, a serial dilution was performed with undiluted vitreal material of two enucleated eyes and sent to L1 for MAT and PCR. The results of the PCR indicated a strong conformity between L1 and L2 (Kappa 0.95), both laboratories concurrently revealed 52 positive and 31 negative results and only two specimens showed deviating results. The MAT in L1 was positive in 51% of the vitreal samples tested, whereas only 41% of the vitreal samples were tested positive in L3. The conformity was, moreover, serovar-and breed-dependent. The Kappa was 0.67 when only including serovar Grippotyphosa, and was 0.82 for serovar Pomona (Tab. 5). Warmblood horses displayed a Kappa of 0.56 between L1 and L3, whereas the Kappa for the Icelandic horses was 0.91 between L1 and L3. The cultivation of leptospires was successful in 16 % of the vitreal specimens. The dilution of vitreal samples was measured to range between 1 and 2.1 with a standard deviation of 1.68. Overall, 67 vitreal samples were tested simultaneously in all three laboratories. A positive result in at least one of the tests performed occurred in 57 % (38), whereas 43 % (29) of the vitreal specimens were tested negative in all five tests performed (PCR in L1 and L2, MAT in L1 and L3, and culture in L3). The variation of agreement of the MAT between serovar Grippotyphosa and serovar Pomona and between Warmblood and Icelandic horses in L1 and L3 might be account...

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Acute Aminoglycoside Retinal Toxicity In Vivo and In Vitro

Cited by 52 publications

References 23 publications

Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa

Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa

Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

Detection of intraocular leptospiral DNA, antibodies and Leptospira spp. in horses with equine recurrent uveitis in different laboratories

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